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Neuroscience lecture notes
Chapter 1: introduction
Animism: the belief that things were animated by spirits
The feeling of consciousness arose from the fact that we are aware of our own existence.
The mind body problem
Dualism: the mind and brain (body) are treated as 2 separate entities; they are fundamentally different.
The body is made of matter, but the brain isn’t.
Monism: everything in the universe consists of matter and energy and that the mind is a phenomenon
produced by the working of the nervous system.
It is believed that once we understand the workings of the human body, than the mind-body problem
will be solved. All that we can detect in the lab are physical things.
Understanding human consciousness: a physiological approach
Consciousness: refers in this text to the fact that humans are aware of- and can tell others about- our
thoughts, memories, perceptions and feelings. It can be altered by changes in the structure or chemistry
of the brain; it is a physiological function, just like behaviour. Consciousness and the ability to
communicate seem to go hand in hand, it might event have given rise to consciousness, it allows us to
think and to be aware of our own existence.
Blind sight: the ability of a person who cannot see objects in his or her blind field to accurately reach for
them while remaining unconscious of perceiving them; caused by damage to the mammalian visual
system. Thus our behaviour can arise from things that we are completely unaware of. The brain contains
more than one area to process vision; the mammalian system, and the primitive system, which is
devoted to controlling eye movement and bringing our attention to sudden movements that occur off
to the side of our field of vision. Thus consciousness isn’t a general property of all parts of the brain. The
parts that are related seem to play a role in our ability to communicate, the primitive system it outside
consciousness.
Split brains: disconnecting parts of the brain involved with perceptions from parts that are involved with
verbal behaviour also disconnects them from consciousness. The surgery is done for people with severe
epilepsy that can’t be controlled by drugs. In these people nerve cells in one side of the brain become
overactive, and the over-activity is transmitted to the other side of the brain by the corpus callosum.
Both sides of the brain then engage in wild activity and stimulate each other causing a seizure.
Neurosurgeons prevent this from happening by cutting the corpus callosum. These patients have been
studied by Gazzinga.
Cerebral hemispheres: the 2 symmetrical halves of the brain that constitute the major part of the brain.
Corpus callosum: the largest commissure of the brain, interconnecting the areas of the neo-cortex on
each side of the brain. It allows for the connection between the 2 hemispheres, so that each of them is
able to share the information.
After a split brain operation, the 2 hemispheres behave independently. It is known that the left
hemisphere produces speech; their left hand seems to have of a mind of its own; the right hemisphere
controls the left hand. Bizarre thing with smell: when asked to pick up something they smelled with only
the right nostril with their left hand, they are able to; but with the right hand, they are unable. They
can’t tell what they sniffed.
If the information doesn’t reach this part of the brain, then information doesn’t enter consciousness.
Unilateral neglect: a syndrome in which people ignore objects located toward their left and the left
sides of objects located anywhere; most often caused by damage to the cortex of the right parietal lobe,
which its primary function consists of putting together information and the location of the parts of the
body with the location of objects in space around us. They can see and feel things to their left, but
ignores such stimuli; they aren’t conscious of it. Damage to the left parietal lobe produces very mild
neglect.
Experiment: the fMRI scans showed increased activity in the parietal lobe and then, as the subjects
began to experience the rubber hand as belonging to their body, in the premotor cortex, a region of the
brain involved in planning movement. When the rubber hand wasn’t identified as their own, the
premotor cortex didn’t become activated. When the parietal cortex thought that sight and feelings were
congruent, they sent signal to the premotor cortex, which gave rise to the feeling of ownership of the
rubber hand. When a knife was pointed towards the rubber hand, a region associated with pain
anticipation became activated and also a region that is activated when a person feels the urge to move.
When we will understand the language processes of our brain, we may go a long way in the discovery of
what consciousness is.
The nature of physiological psychology
Wundt: Principles of Physiological Psychology
The ultimate function of the nervous system is behaviour.
Sometimes thinking doesn’t produce behaviour, but is has evolved because it permits us to perform
complex behaviour which allow us to achieve our goals.
The goals of research
Generalization: a type of scientific explanation; a general conclusion based on many observations of
similar phenomena.
Reduction: a type of scientific explanation; a phenomenon is described in terms of the more elementary
processes that underlie it.
Physiological psychologists explain behaviour by studying the physiological processes that control it.
Sometimes psychological processes can be understood by physiological mechanisms. The relationship is
particularly true of complex phenomena.
Findings indicate that the ability to recognize a spoken word and to spell it call on related brain
mechanisms. Reading comprehension can take 2 routes: one that is related to speech sounds and one
that is primarily a matter of visual recognition of whole words.
Biological roots of physiological psychology
Many ancient cultures (Egyptian, Chinese, Indian) considered the heart to be the seat of thought and
emotions. The ancient Greeks did to, but Hippocrates concluded that this role should be assigned to the
brain. Aristotle didn’t share this view; he thought that the brain served to cool the heart’s passions.
Galen thought that Aristotle’s view didn’t make sense, for the brain wouldn’t be so far from the heart.
He dissected brains. Alcmaeon agreed with Hippocrates and Galen.
Descartes, the father of modern philosophy, tried to solve the mind-body interaction. The world is a
mechanical entity set in motion by God, ran its course without divine interference. To understand the
world, one had to know how it was constructed. Animals were mechanical devices, and the human body
was a machine. He called reflexes an automatic, stereotypical movement that is produced by the direct
result of a stimulus; it doesn’t require the participation of the mind. He believed that each person
possessed a mind: a uniquely human attribute that wasn’t subject to the laws of the universe. He was
the 1st to suggest that there exists a link between mind and brain. He believed that the mind controlled
the movement of the body, through its sense organs, supplied the mind with information. The mind
interacts with the body through the pineal body, a small organ on top of the brain stem, buried beneath
the cerebral hemispheres. When the mind decided to perform an action, the pineal body would tilt in a
particular direction, causing fluids to flow from the brain into nerves. His work was influenced by
statues, and dismissed quickly.
Model: a mathematical or physical analogy for a physiological process (computers for the functioning of
the brain. Descartes was the 1st one to use a mechanical model to illustrate a human process.
Descartes’ model could be tested empirically, and it didn’t take long for biologist to prove him wrong.
Galvani: electrical stimulation of a frog’s nerve caused contraction of the muscle to which it was
attached. This contraction occurred even when the nerve and muscle were detached of the rest of the
body; the ability to send a message is a property of the tissue itself.
Muller: removed and isolated animal organs, testing their response to various chemicals. He set the
stage for direct experimentation on the brain.
Doctrine of specific nerve energy: Muller’s conclusion that because all nerve fibres carry the same type
of message, sensory information must be specified by the particular nerve fibres that are active. We
perceive messages from different nerves in different ways, and the messages occur in different
channels, the brain must be functionally divided.
Experimental ablation: the research method in which the function of the part of the brain is inferred by
observing the behaviours an animal can no longer perform after that part has been damaged. (method
by Flourens, who claims to have discovered parts of the brain responsible for heart rate, breathing,
purposeful movements, visual and auditory reflexes).
Broca: observed the behaviour of people whose brains had been damaged by strokes resulting in the
loss of the ability to speak; portion on the left cerebral cortex are responsible for the production of
speech.
Fritsch and Hitzig: stimulation (dog) of different portions to a specific region of the brain caused
contraction of specific muscles on the other part of the body. This region is referred to as the primary
motor cortex, with which many parts of the brain interact.
Hemholtz: the law of conservation of energy, invented the ophtalmoscope, devised a theory of color
vision and color blindness. He studied audition, music... He didn’t agree with his mentor Muller’s view
that a vital non-material force controls the organs, and thought that all aspects of physiology are
mechanistic, subject to experimentation. He was the 1st to measure the speed of conduction through
nerves (90feet/sec); thus neural conduction is more simple the electrical signals.
Natural selection and evolution
Darwin formulated the principles of natural selection and evolution
Materialism: rational behaviour can be fully explained by the workings of the nervous system without
the need to refer to a non-material mind.
Functionalism and the inherence of traits
An organism’s characteristics have functional significance.
Functionalism: the principle that the best way to understand a biological phenomenon is to try to
understand its useful functions for the organism. The history of species must be understood. We can’t
say the physiological mechanisms have a purpose, but they have functions which can be determined.
Natural selection: the process by which inherent traits that confer a selective advantage become more
prevalent in a population. It would be the basis for the development of species. It can act on behaviour
indirectly.
Mutation: a change in the genetic information contained in the chromosomes, which can be passed on
to an organism’s offspring producing genetic variability, which is a great advantage.
Selective advantage: a characteristic of an organism that permits it to produce more than the average
number of offspring of its specie.
It is important to ask ourselves if a certain finding makes sense from an evolutionary point of view.
Evolution of the human specie
Evolution: a gradual change in the structure and physiology of plant and animal species- generally
producing more complex organisms- as a result of natural selection.
A mass extinction occurred about 248M years ago and killed 95% of all species, marked the end of the
Permian period. Cynodont, the ancestor of mammals survived. 65M years ago, extinction at the end of
the Cretaceous occurred and killed the dinosaurs, the era of mammals began (Cenozoic period). Natural
selection favoured trees that encased their seeds in sweet, nutritious food that would be eaten. This
gave rise to the advantage of colour vision. Hominids appeared in Africa, they used tools and produced
clothing and they discovered the many uses of fire. Homo erectus was the 1st to leave Africa 1.7M years
ago scattered across Europe and Asia. Homo Neanderthalis appeared in Western Europe. Homo sapiens
evolved in East Africa 100K years ago. They interacted with the Homo N. They disappeared 10k years
ago.
Evolution of large brains
Humans: agile hands, color vision, fire, bipedalism (allowed them to walk long distances, allowed to
bring food), and language. All of this required a large brain, which requires a large skull, and an upright
posture limits the size of a woman’s birth canal (good luck giving birth). The baby’s brain continues to
grow after birth; all mammals require parental care while the neural system develops. Thus, evolution
produced a larger brain with an abundance of neural circuits that could be modified by experience.
Some animal’s brains are larger than ours, but this doesn’t matter, our brain is 2.3% of our body weight,
while an elephant’s brain is only 0.2%, but the shrew’s brain is 3.3%. OMG there must be something
wrong. The size of the brain doesn’t have to be proportional with the size of the body. Intelligence
depends on the quality of the neural connections.
Brains also vary in the number of neurons found in each gram of tissue. Primate’s brains have more
neurons for the size per gram than rodent brains. Allowing more time for growth may be responsible for
this increase; the prenatal period of cell division in the brain is prolonged in humans (brain weighs 350 g
and contains 100G neurones). Neurogenesis is very slow, but connections form after birth, the brain
reaches its adult size in late adolescence and weighs about 1400g.
Neoteny: a slowing of the process of maturation, allowing more time for growth; an important factor in
the development of large brains.
Ethical issues in research with animals
Most of the research is done on animals. Most societies have very strict regulations about the care of
animals and require approval of the experimental procedures that are used on them. These animals
might even be better treated than with pet owners, because of the strict regulations.
Moral absolutes can’t be treated logically; they can either be rejected or accepted. 0.3% of the animals
are used in research, but 63.6% of pages in activists books are dedicated to them. The cause of animal
use in research is the only essential one, it is needed for progress. A lot would be lost if research was
stopped, much to the detriment of research and treatment of numerous diseases.
If a blood vessel leading to the brain is blocked for a few minutes, the part of the brain that is nourished
by that vessel dies. Research on this requires animals.
Research on animals has produced important discoveries about the possible causes or potential
treatment of several neurological and mental disorders.
Tissue culture and computers can’t be a substitute for living organisms.
e.g. Rhesus monkeys and polio, Parkinson’s disease with L-DOPA.
The pursuit of knowledge is itself a worthwhile argument.
Humans and non-human subjects for research
Humans: language, report subjective experiences, they have a human brain
Animals: the underlying mechanisms of behaviour are similar across species and easier to study in
nonhuman subjects; evolutionary continuity; interest in animals for their own sake; provide
experimental control.
Experimental approaches to understanding behaviour
1- Invasive physiological research methods
2- Behavioural paradigm that assess constituent cognitive processes
3- Pharmacological research methods
4- Genetic engineering
5- Visualizing the living human brain
6- Neuropsychological testing
Careers in neuroscience
Physiological psychologists: a scientist who studies the physiology of behaviour, primarily by performing
physiological and behavioural experiments with laboratory animals, sometimes with humans as well,
using non-invasive techniques. They are also called behavioural neuroscientists; this field is in the realm
of neuroscience (from molecular genetics to the study of social behaviour). Other overlapping fields are
neurology (physicians) and cognitive neuroscience (Ph.Ds in psychology with a specialized training in the
techniques of the field of neurology)
Chapter 2: structure and functions of the cells of the nervous system
Major divisions of the nervous system
CNS: the brain and the spinal cord
PNS: everything outside the skull and spinal cord
Afferent: going towards - Efferent: going away
Somatic: interacts with external environment. Afferent nerves: carry sensory signals from the sensory
organs to the CNS. Efferent nerves: carry motor signals from the CNS to skeletal muscles.
Autonomic: regulates the body’s internal environment. Afferent nerves: carry sensory information from
the internal organs to the CNS. Efferent nerves: carry sensory information from the CNS to the internal
organs.
Sensory neurons: a neuron that detects changes in the external or internal environment and sends
information about these changes the CNS
Motor neurone: a neurone located within the CNS that controls the contraction of a muscle or the
secretion of a gland
Interneuron: a neurone located entirely in the CNS. Local interneurons form circuits with nearby
neurons and analyse small pieces of information. Relay interneurons connect circuits of local
interneurons in one region of the brain with those in other regions.
Basic structure of the cell
Soma: the cell body, the metabolic centre of the neuron
Dendrites: treelike extensions of the soma. They receive information from other cells and carry it to the
soma
Terminal buttons: button-like endings of the axon branch. They release neurotransmitters after
receiving action potential. They connect with another neuron via the synapse
Myelin sheath: a fatty material insulating the axon. It prevents messages spreading between adjacent
axons.
Axon: projects from the soma. It carries information from the soma to the terminal buttons. It carries
the action potential.
Synapse: a junction between the terminal button of the sending neuron and a portion of the dentritic
membrane of the receiving neuron. Communication proceeds in one direction only: from the terminal
button to the membrane of the other cell.
Classes of neurones (classified according to how their axons and dendrites leave the soma)
Multipolar: have one axon and many dendrites attached to its soma. Several dendrites allow for
integration of a great of information. The most common form of neuron in the CNS
Bipolar: 2 processes leaving the soma. At one end, there is a single dendrite tree. They transmit sensory
information to the CNS
Unipolar: have one process extending from the soma; the axon then divides into 2 branches. They
detect touch, temperature changes, pain and other sensory events that affect the skin. Dendrites are
outside the CNS and the terminal buttons are inside the CNS.
Interneurones: link sensory and motor neurons.
Internal structure (inside the soma)
Membrane: defines the outer boundary of the cell. It is embedded with protein molecules that have
special functions. It consists of a double layer of lipids. Some proteins detect substances outside the cell
and pass information about the presence of these substances to the interior of the cell. Others control
access to the interior of the cell, and others act as transporters. Proteins often serve as enzymes,
catalyzing thus controlling certain chemical reactions.
Cytoplasm: a gelatinous, semi-transparent fluid in which organelles are suspended. It varies across cell
type.
Mitochondria: double membraned organelles that are the site of energy production. They produce ATP
that cells use as their immediate source of energy. They contain their own DNA and reproduce
independently from the rest of the cell.
Nucleus: houses the nucleolus and the chromosomes
Endoplasmic reticulum: parallel layers of membrane. Rough endoplasmic reticulum contains ribosomes
and is involved in production of proteins that are secreted by the cell. Smooth endoplasmic reticulum is
the site of synthesis of lipids and provides channels for the segregation of molecules involved in various
cellular processes.
Golgi apparatus: a complex of parallel membranes in the cytoplasm that wraps the products of the
secretory cell. It is a special form of smooth reticulum.
Exocytis: the secretion of a substance by a cell through vesicles; the process by which neurotransmitters
are secreted.
Lysosomes: produced by the Golgi apparatus, it is surrounded by a membrane; contains enzymes to
break down waste products
Cytoskeleton: formed of microtubules and other protein fibers, linked to each other and forming a
cohesive mass that gives a cell its shape.
Microtubules: a long strand of bundles of protein filaments (13) arranged around a hollow core; part of
the cytoskeleton and involved in transporting substances from one place within the cell.
Axoplasmic transport: an active process by which substances are propelled along microtubules that run
the length of the axon.
Anterograde: in a direction along an axon from the terminal buttons toward the cell body. Retrograde:
the inverse direction.
PROTEIN SYSTHESIS
The nucleolus is responsible for the production of ribosomes, which are involved in protein synthesis.
The chromosomes (DNA), when active, cause production of mRNA (transcription) which leaves the
nuclear membrane and attaches ribosomes, where it causes production of a particular protein.
The genome is the sequence of nucleotide bases located on the chromosomes; it provides information
necessary for the production of all proteins in the body. There are a lot of non-coding elements in it. The
number of such sequences correlates with the complexity of an organism. The non-coding regions are
much conserved (90% correlation) across species (human and puffer fish). These non-coding sequences
were found to be near coding elements. Mutations in non-coding regions appear to have played a role in
the development of our large brains.
ncRNA: doesn’t encode for protein, but has a function of its own. They are a constituent of the
spliceosome. They also attach and modify proteins that regulate gene expression
Supporting cells
Neuroglia or Glia cells: the supporting cells of the nervous system. They isolate the neurons.
Astrocyte: a glial cell that provides physical support and cleans up debris in the brain through
phagocytis. They control chemical composition of the extra cellular fluid and nourish the neuron from
capillaries to their cytoplasm where glucose is broken down to lactate, then to the cytoplasm of neurons
(they also produce glycogen-glucose-lactate). They establish structures responsible for communication
between neurones.
Oligodendrocytes: provide support to the axon of the cell and produce the myelin sheath ( 80% lipid,
20% protein) which forms a tube around the axon for insulation. The sheath isn’t continuous; it is a
series of segments (up to 50). The exposed axon is called the node of Ranvier.
Microglia: are the smallest of the glial cells. They provide an immune system for the brain and protect
the brain from invading microorganisms. They phagocyte the dead neurons, they are responsible for the
inflammatory response to brain damage.
Schwann cells: a cell in the PNS that is wrapped around a myelinated axon, providing one segment of its
myelin sheath. They can aid the digestion of a dead or dying axon, and then arrange in a series of
cylinder that act as guide for the reconstruction of the axon. The stump of the severed axons grow
sprouts in all directions, the sprout will grow in the cylinder of the Schwann cell. The axons could then
reattach to their associated organs. In the CNS the axons will grow, but they will encounter astrocyte
scarring tissue. In phase one of regrowth, the axons are elongated; in phase two, terminal buttons are
produced once the axon has reached its destination. The immune system of someone with multiple
sclerosis attacks only the myelin produced by the oligodendrocytes.
The blood brain barrier
Ehrlich: if we inject a blue dye, all the tissues will become blue except the brain and spinal cord. If this
fluid is injected in the ventricles of the brain, all the CNS will be dyed.
The blood-brain barrier: a semipermeable barrier (selective) between the blood and the brain
produced by the cells in the wall’s of the brain’s capillaries (no gaps allowing exchanges in the
capillaries). Other substances must be actively transported through the capillaries by special proteins.
It provides a balance between substances within neurones and in the extracellular fluid. An imbalance
can disrupt the transmission of messages thus affecting brain function. It impedes the passage of toxic
substances.
Area postrema: a region of the medulla where the blood-brain barrier is weak; poisons can be treated
there and can initiate vomiting.
Communication within a neurone
Withdrawal reflex: dendrites of a sensory neurone detect painful stimulus, it sends messages down the
axon to the terminal buttons in the spinal cord which release neurotransmitters that excites the
interneuron, causing it to send messages down its axon. The terminal buttons of the interneuron release
a neurotransmitter that will excite the motor neuron, which sends messages down its axon, which joins
a nerve and travel to a muscle. When the motor neuron’s neurotransmitters are released, the muscle
contracts.
The role of inhibition: the brain can overrun the withdrawal reflex by sending messages to the spinal
cord where it reaches an inhibitory interneuron which releases an inhibitory neurotransmitter which
decreases the activity of the motor neuron.
Measuring electrical potential of axons
Recording information from the giant axon of a squid (0.5mm diameter): Electrodes are used to record
the electrical activity of the signal, An electrode is in the sea water, and a microelectrode made of thin
glass tubing, filled with KCl. It can be seen the membrane potential, the electrical charge across the cell
membrane; the difference in electrical potential inside and outside the cell, is of -70mV. To study the
message, an oscilloscope, a sensitive voltmeter that can detect electrical fluctuation is used.
A graph of this can be made where the x axis represents time and the y axis represents membrane
potential. A straight line is drawn at -70mV , which corresponds to the resting potential (the inside of
the axon is negative, it is polarized) A stimulator can disturb it by passing current through another
microelectrode inserted in the axon. Passing a positive charge causes a depolarization, reducing the
charge of the membrane. When the electrical current is strong enough to reach the threshold of
excitation, the value of the membrane potential that must be reached to produce an action potential (60mV), then a rapid reversal of the membrane potential, called the action potential is triggered. Its peak
is at 30mV, once it is reached, the membrane potential goes back to normal, but 1st overshoots the
resting potential, becoming more negative. The membrane is then hyperpolarized. The overall process
takes about 2msec.
The membrane potential: the balance of diffusion and electrostatic pressure
Diffusion: ions move from a more concentrated medium to a less concentrated medium
Electrostatic pressure: the attractive or repulsive forces between ions (solutions that electrolyse in H20)
The membrane potential is maintained by the balance of diffusion and electrostatic pressure. Both
forces are influenced by the concentration of ions in the intracellular and extracellular fluids, which
contain different ions. There are 4 important ions (A-,K+,Cl-,Na+)
Intracellular fluid: negatively charged, predominant ions: A-: organic anion: negatively charged proteins
and intermediates products of the cell’s metabolic processes, they are only found in the intracellular
fluid), K+
Extracellular fluid: positively charged: predominant ions: Na+, and ClA-: unable to pass through the membrane, thus it stays there
K+: forces of diffusion tend to push it outside the cell. However, the outside of the cell is positively
charged, thus the electrostatic pressure pushes the cation inside. The 2 forces balance, and K+ stays.
Cl-: diffusion pushed it inwards, electrostatic pushes it outward. The 2 forces balance out
Na+: pushed in the cell by forces of diffusion, but electrostatic pressure doesn’t force it to stay outside
the cell, it is instead attracted by the negative charge inside the cell. The sodium-potassium pump,
protein molecules embedded in the membrane and energy driven by ATP (40% of the neuron’s
metabolic resources are used by them), continually pushed it outside the axon. These sodium-potassium
transporters continuously exchange Na+ for K+; pushing 3 Na+ for 2 K+. Because the membrane isn’t
very permeable to Na+ (it is 100x more permeable for K+ than Na+), these transporters very effectively
keep the intracellular concentration of Na+ low. By transporting K+ inside the cell, they increase its
concentration.
The action potential: caused by a sudden influx of Na+ into the cell
Ion channels: protein assembly that selectively lets ions flow, they are ion-selective. The permeability of
the membrane for a particular ion is determined by the number of ion channels that are opened. (they
can allow up to 100M ions per second).
Voltage-dependent ion channels: an ion channel that opens or closes according to the value of the
membrane potential. Important on a long-term basis.
1- When the excitation threshold is reached and the action potential begins, the voltage-dependent
sodium channels open, triggered by a depolarization, and cause Na+ to rush inside the cell (increase of
0.0003%). The influx of positively charged Na+ produces a rapid change in the membrane potential,
from -70mV to +40mV.
2- The voltage-dependent potassium channels require a greater depolarization before they open than the
sodium ones. Thus they begin to open later, causing K+ to start leaving the cell.
3- When the action potential reaches its peak (1msec), the sodium channels become refractory; they are
blocked and can’t open again until the membrane reaches its resting potential. At this time, no more
Na+ can enter the cell.
4- The potassium channels are opened, K+ can move freely through the membrane. At this time, the
membrane potential is positive, so K+ is driven out of the cells by diffusion and electrostatic pressure.
This flow causes the membrane potential to return toward its normal value. As it does so, the potassium
channels begin to close again.
5- Once the membrane potential is back to normal, the sodium channels reset, so that another
depolarization can cause them to open again.
6- The membrane overshoots its resting value, and gradually returns to normal as the potassium channels
close. Eventually, the sodium-potassium transporters remove the Na+ that leaked in and the K+ that
leaked out.
Conduction of the action potential: the movement of information along the axon
All-or-none law: the principle that once an action potential is triggered in an axon, it is propagated
without decrement to the end of the axon.
The conduction occurs in a unidirectional manner; it always starts at the end that is attached to the
soma.
It is not the action potential that is the basic element of information; it is the rate of firing of the neuron.
This principle is the rate law
In a myelinated axon, stimulus produce a disturbance in membrane potential that becomes
progressively smaller as it moves away from the point of stimulation. When the subthreshold
stimulation is sent, it is passive; no channels open
Cable properties: the passive conduction of electrical current is a decremental fashion – down the
length of an axon.
Schwann cells wrap tightly around the axon, leaving no place for extracellular fluid, thus Na+ can never
flow in a myelinated axon. Only at the nodes of Ranvier can there be contact. The axon passively
conducts the electrical disturbance from the action potential to the next node of Ranvier. The
disturbance gets smaller, but it stays big enough to reach the next node where it get retriggered
Saltatory conduction: conduction of action potentials by myelinated axons. The action potential
appears to jump from one node of Ranvier to the next.
Advantages of myelination
Sodium ions enter axons during action potentials. Sodium-potassium transporters must be located along
the entire length of the unmyelinated axon, because Na+ enters. Myelinated axons expend much less
energy, because there are less pumps, because there is less sodium to be expelled (less enters)
Speed: the transmission between nodes is very fast. The fastest action potential is 20um in diameter and
can reach speeds of 432 km/h.
Communication between neurones
Synaptic transmission: the transmission of messages from one neuron to another through a synapse by
means of neurotransmitters released by the terminal buttons, which diffuse in the gap.
Post-synaptic potential: alterations in the membrane potential of a post-synaptic neuron, produced by
the liberation of a neurotransmitter, which alter the rate of firing of the neuron.
The neurotransmitter (ligand) binds with the binding site at the membrane of the post-synaptic neurone
Structure of synapse
3 types: axodendritic (on dendrites), axosomatic (on soma), axoxonic (on axon)
Dendritic spines: a small protrusion on the surface of a dendrite with which a terminal button of
another neuron forms a synapse.
Presynaptic membrane: the membrane of a terminal button that lies adjacent to the post-synaptic
membrane and through which the neurotransmitter is released.
Post-synaptic membrane: the cell membrane opposite the terminal button in a synapse; the membrane
of that cell receives the message.
Synaptic cleft: the space between the presynaptic membrane and the post-synaptic membrane. It is
filled with extracellular fluid.
Synaptic vesicles: contains molecules of neurotransmitter. They attach to the pre-synaptic membrane
and release neurotransmitters in the synaptic cleft. Transporting proteins fill the small vesicles with
neurotransmitters and trafficking proteins are involved in the release of neurotransmitter and recycling
of vesicles. Most of them are located near the membrane. Small vesicles are also produced by the Golgi
apparatus, and are carried by fast axoplasmic transport to the terminal button. Large vesicles are only
produced by the soma, and are transported through the axoplasm to the terminal buttons.
Specialized protein molecules detect the presence of neurotransmitters in the cleft, which cause the
post-synaptic density
Release of a neurotransmitter
A number of small vesicles located just inside the pre-synaptic membrane become docked against the
pre-synaptic membrane and break open, spilling their content in the cleft. Docking occurs when clusters
of protein molecules attach to other protein molecules located in the pre-synaptic membrane.
The release zone of the presynaptic membrane contains voltage-dependent calcium channels. When the
membrane of the terminal button is depolarized by an action potential, the Ca 2+ channels open,
causing Ca 2+ located in highest concentration in the extracellular fluid, to enter the cell. Ca 2+ is
essential for the release of the neurotransmitter. Ca 2+ enters and bind with the protein embedded in
the membrane of synaptic vesicles docked at the release zone. The fusion pores open, the membrane
can fuse together, and the neurotransmitter is released.
Release-ready vesicles: (1%) docked against the inside of the membrane, ready to release their content.
Recycling pool vesicles: (10-15%); Reserve pool vesicles: (85-90%). If the axon fires at a low rate, only
the release-ready vesicles will be used. If the rate of firing increases, the vesicle from the recycling pool,
and finally from the reserve pool will be called on.
When the release-ready vesicle release their content, the fusion pore closes, they break away from the
membrane and get filled with neurotransmitter again (kiss and run). Other vesicles merge and release
and constantly lose their identities. The recycling process of reserve vesicles is done through bulk
endocitosis.
Activation of receptors
Postsynaptic receptor: s receptor molecule in the post-synaptic membrane that contains a binding site
for the neurotransmitter, which will hyper or depolarize the membrane.
Neurotransmitter-dependent ion channel: an ion channel that opens when a molecule of
neurotransmitter binds with a post synaptic receptor. It leads to changes in the membrane potential.
Ionotropic receptor: a receptor that contains a binding site for a neurotransmitter and an ion channel
that opens when a molecule of neurotransmitter attaches to its binding site. It is direct. They are
sensitive to Ach and contain sodium channels.
Metabotropic receptor: a receptor that contains a binding site for a neurotransmitter; activates an
enzyme that begins a series of events that opens an ion channel elsewhere in the membrane of the cell
when a molecule of neurotransmitter attaches to the binding site. It is indirect.
G protein: a protein coupled to a metabotropic receptor; conveys messages to other molecules when a
ligand binds with and activates the receptor.
When a molecule of neurotransmitter binds with the receptor, the receptor activates the G protein,
located inside the membrane next to the receptor, which activates an enzyme that stimulates the
production of the second messenger (cAMP). Molecules of the second messenger travel through the
cytoplasm, attach themselves to nearby ion channels and causes them to open. Second messengers play
an important role in both synaptic and nonsynaptic communication.
Post-synaptic potentials
They can be either depolarizing (excitatory), or hyperpolarizing (inhibitory). Their nature is determined
by the characteristics of the post-synaptic membrane- in particular by the type of ion channels they
open.
There are four major types of ionotropic neurotransmitter-dependent ion channels that are found in the
post-synaptic membrane: Na+, K+, Cl-, Ca2+
Na+: influx of Na+ causes a depolarization: EPSP: excitatory post-synaptic potential
K+: when it leaves the cell, it causes a hyperpolarization: IPSP: inhibitory post-synaptic potential
For Cl- and Ca2+: their influence depends on the membrane potential
Cl-: if the membrane is at resting potential, nothing will happen; the forces balance it out. If the
membrane has been depolarized by the activity of excitatory synapses, then the opening of chloride
channels will allow it to enter the cell, causing the membrane potential to return to normal. Cl- serves to
neutralize the effects of the EPSP
Ca2+: they act like Na+ channels, producing EPSPs, but can also trigger the migration of synaptic vesicles
and the release of neurotransmitter. In the dendrites of the post-synaptic cell, it binds with and
activates certain enzymes.
Termination of post-synaptic potentials
They are controlled by reuptake and enzymatic deactivation
reuptake: the re-entry of a neurotransmitter just liberated by a terminal button back through its
membrane, thus terminating the post-synaptic potential. The membrane contains special transporter
molecules that force molecules of neurotransmitter from the synaptic cleft directly into the cytoplasm.
The post-synaptic receptor are only briefly exposed to the neurotransmitter.
Enzymatic deactivation: the destruction of a neurotransmitter by an enzyme after its release. E.g. the
destruction of acetylcholine by acetylcholinesterase, which cleaves it in its constituents: choline and
acetate.
Ach: a neurotransmitter found in the brain, spinal cord, and parts of the PNS responsible for muscular
contraction. AChE is extremely affective Ach breaker.
Myasthenia gravis: progressive muscular weakness. Treated with physostigmine, with deactivates AChE.
It is auto-immune and currently has no cure. The immune system destroys the Ach receptors.
Effects of post-synaptic potentials: neural integration
The rate at which the neurone is firing is determined by the relative activity of excitatory (increases
likelihood of firing) and inhibitory (decreases) synapses on the soma and dendrites.
Neural integration: the process by which inhibitory and excitatory postsynaptic potentials summate and
control the rate of firing of the neuron.
The release of neurotransmitter EPSPs in the dendrites which are transmitted, down the dendrites,
across the soma, to the axon hillock located at the base of the axon. If the depolarization is still strong
enough at that point the neurone will fire.
If several inhibitory synapses are active at the same time as an EPSP, the IPSP will diminish the size of
the EPSP and prevent the axon from firing.
Note than neural inhibition will not always produce behavioural inhibition; inhibition of the inhibitory
neurones makes the behaviour more likely to occur, and excitation of neurones that inhibits the
behaviour suppresses the behaviour (e.g. dream).
Autoreceptor: a molecule on the neuron that responds to the neurotransmitter released by that
neuron. They don’t produce changes in the membrane potential of the terminal button; they regulate
internal processes, they can control the synthesis and release of neurotransmitters. They are
metabotropic. In most cases its effects are inhibitory. It plays a role in the control of the amount of
neurotransmitter released.
Other types of synapses
Axoaxonic synapses don’t contribute directly to neural integration; they alter the amount of
neurotransmitter released. They can produce presynaptic modulation: inhibition or facilitation.
Presynaptic inhibition: The actions of a presynaptic terminal button in an axoaxonic synapse; reduces
the amount of neurotransmitter released by the postsynaptic terminal button.
Presynaptic facilitation: The actions of a presynaptic terminal button in an axoaxonic synapse;
increases the amount of neurotransmitter released by the postsynaptic terminal button.
Very short neurones lacking axons form dendrodendritic synapses, and they don’t transmit information
from place to place in the brain; they perform regulatory functions. Little is known.
Other neurones can form dendrodendritic synapses. Some of them are chemical, and others are
electrical; the membranes meet and almost touch forming a gap junction. Membranes of both sides
contain ion channels and allow ions to diffuse. Most gap junctions in vertebrates are of this type,
although others can be axosomatic and axoaxonic. Gap junctions are common in invertebrates.
Nonsynaptic chemical communication
Neuromodulators: a naturally secreted substance that acts like a neurotransmitter except that it isn’t
restricted to the synaptic cleft, but diffuse through the extracellular fluid. They are chemicals released
by neurons, and most of them are peptides. They are secreted in large amounts, for a longer period and
can influence many neurones in a particular part of the brain
Hormones: a chemical substance secreted by the endocrine gland, which releases its content into the
extracellular fluid that has a direct effect on the targeted cells and organs.
Steroids: derived by cholesterol, it affects their target cells by attaching to receptors found within the
nucleus.
Chapter 3: structures of the nervous system
Basic feature of the nervous system (for terminology and images see lecture slides)
The brain is encased in a bony skull and floats in the cerebrospinal fluid (CSF), it is chemically guarded by
the blood-brain barrier. The brain needs constantly 20% of the blood flow, because it can’t store its own
fuel.
Meninges (menix): composed of 3 layers of tough protective tissue that surrounds the brain and the
spinal cord.
1- Dura matter: the outermost of the meninges; tough and flexible, but unstretchable.
2-arachnoid membrane: gets its web-like appearance from the arachnoid traberculae that protrude
from it. It is soft, and spongy
3- Pia matter: closely attached to the brain, it follows every convolution it has. The smaller surface
blood vessels of the brain and spinal cord are contained within it.
Subarachnoid space: between the arachnoid membrane and the pia matter with the CSF that fills it
along with the ventricular system of the brain.
The PNS is covered only by the dura and pia matter that fuse and form a sheath the covers the spinal
and cranial nerves and the peripheral ganglia.
The ventricular system and production of the CSF
Because the brain bathes in liquid its weight goes down to 80g; thus the pressure and the base of the
brain is greatly diminished. The CSF also reduce the shock that would occur by sudden movements of
the head.
Ventricles: hollow spaces in the brain filled with CPS.
The lateral ventricles are the largest and comprise the 1st and 2nd ventricles, and are connected the 3rd
ventricle located in the center of the diaencephalon (midline of the brain; its walls divide the
surrounding part of the brain into symmetrical halves. A bridge of neural tissue called the massa
intermidia crosses through the middle of the 3rd ventricle and serves as a reference point). The cerebral
aqueduct, a long tube connects the 3rd ventricle to the 4th ventricle, which is located between the
cerebellum and the dorsal pons, in the center of the metencephalon.
Choroid plexus: the highly vascular tissue that protrudes into the ventricles and produces CSF; its total
volume is of 125 ml and it has a half life of 3 hours. Thus the choroid plexus produces this amount
several times a day.
CSF is produced in the choroid plexus of the lateral ventricles, and flows in the 3rd ventricle. More is
produced there and then flows through the cerebral aqueduct to the 4th ventricle, where more is
produced. The CSF leaves the 4th ventricles through small openings that connect with the subarachnoid
space surrounding the brain. The CSF flows through the subarachnoid space around the CNS, where it is
reabsorbed in the blood supply by the arachnoid granulations. These pouch-shaped structures protrude
into the superior sagittal sinus, a blood vessel that drains into the veins serving the brain.
Obstructive hydroencephalus: a condition in which all or some of the ventricles are enlarged; caused by
an obstruction that impedes the normal flow of the CSF.
The central nervous system
Development if the CNS (starts as a hollow tube)
Development of the nervous system begins 18 days after conception. Part of the ectoderm of the
embryo thickens and forms a plate. Its edges form ridges that curl toward each other along a
longitudinal line, running in a rostral-caudal direction.
By the 21st day, these ridges touch each other and fuse together, forming the neural tube, which give
rise to the brain and spinal cord. The top part of the ridges breaks away from the neural tube and
become the ganglia of the autonomic nervous system.
By the 28th day, the development of the neural tube is closed, and its rostral end has developed 3
interconnected chambers, which become the ventricles, and the tissue that surround them become the
3 major parts of the brain: the forebrain, the midbrain, and the hindbrain.
As development progresses, the rostral chamber (the forebrain) divides into 3 separate parts, which
become the lateral ventricles and the 3rd ventricle. The region around the lateral ventricle become the
telencephalon (end brain), and the regions around the 3rd ventricle become the diaencephalon.
In its final form, the chamber inside the midbrain (mesencephalon) becomes narrow, forming the
cerebral aqueduct, and 2 structures develop in the hindbrain: the metencephalon (after brain) and the
myelencephalon (marrowbrain).
Details of brain development (cortex)
Ventricular zone: a layer of cells that line the inside of the neural tube; contains progenitor cells which
divide and give rise to cells of the CNS. The cerebral cortex develops from the inside out. There are 6
layers – each time a new layer is formed, the cells forming it must pass through all the other layers.
Progenitor cells: cells of the ventricular zone that divide and give rise to cells of the CNS.
Symmetrical division: division of a progenitor cell that give rise to 2 identical progenitor cells increases
the size of the ventricular zone and hence the brain develops from it.
Asymmetrical division: division of progenitor cells that gives rise to a new progenitor cell and a neuron
that will migrate to its final resting place in the brain – lasts about 3 months.
Radial glia: the 1st cells produced by asymmetrical division. They are special glia with fibers that grow
ridially outward of the ventricular zone to the surface of the cortex; providing guidance for neurons
migrating outward during brain development.
Cajal-Retzius (C-R) cells: specialized neurons that establish themselves during cortical development in a
layer near the terminal of the radial glia, just inside the pia matter; secrete a chemical that controls the
establishment of migrating neurons in the layers of the cortex
A set of neurons is produced that forms a layer just beneath the C-R cells, which constitute the 1st inner
most region. As neurogenesis continues, the cells leave the ventricular zone, pass the 1st layer of
neurons, and establish themselves just inside the layer of the C-R cells. Neurons are guided by the radial
glia cells and crawl along radial fibers like amoebas, pushing their way through neurons that were born
earlier and coming the rest against the layer of the C-R cells. Chemicals from these cells cause the
neurons to detach from the radial fibers and establish themselves in the outermost layer of the cortex.
The 1st migration takes one day, and the last on take 2 weeks.
Apoptosis: death of cell caused by a chemical signal that activates a genetic mechanism inside the cell.
When the progenitor cells die by that process, it marks the end of cortical development. Some radial glia
cells appear to undergo that process, but many are transformed in astrocytes or neurons.
Once the neurons have migrated to their final location, they begin to form connections with other
neurons. They grow dendrites and axons, which when they reach their target, form numerous branches,
which find an place on a membrane of the appropriate post-synaptic neuron, grows a terminal button
and establishes a synaptic connection. Attraction between neurons depends on the type of chemical
secreted. The chemical signals that the cells exchange to form the synapse are beginning to be
discovered.
The ventricular zone gives rise to more neurons then needed, they have to compete in order to survive.
(50% don’t) when a presynaptic neuron establishes a synaptic connection, it receives a signal from the
post-synaptic neuron that allows it to survive.
Of course, some of the specialization of the neurons is encoded in the genes. If the progenitor cells are
different, the neurons they will produce will be different as well. Each neuron goes to a definite place in
the brain to perform their function. Specialization in a particular region of the cortex can also be induced
by the axons that provide input to these regions.
By a study on opossum researchers found that the boundaries of specialized regions were different from
those seen in normal brain: the growth of axons from particular regions of the cortex has an effect on
the development of the cortical regions they served.
Experience also affects development. The particular neural circuits that are necessary for stereotopsis
(the fact that each eye receives slightly different information that gives rise to depth perception) will not
develop unless an infant gets to view objects with both eyes at critical periods (somewhere between 1-3
years). Evidence suggests that a certain amount of neuron wiring can occur during adult life (amputation
cases, musicians, blind people who learn Braille).
Recent studies show that neurogenesis occurs even in the adult brain, which contains some stamp cells
that can divide and produce neurons. (Evidence is obtained by radioactively probing one of the
nucleotides necessary to produce the DNA for neurogenesis. It occurs only in 2 parts of the adult brain:
the hippocampus and the olfactory bulb (new olfactory experiences can increase the survival rate of the
cells in that region, and training on a learning task can enhance neurogenesis in the hippocampus.
Depression and exposure to stress suppresses this process. Unfortunately, there is no evidence that
suggests the growth of new cells that can replace damaged brain tissue.
Evolution of the human brain
Genetic duplication is an important process in the evolution to form more complex, more
interconnected brains. If those duplication arise in the cells that give rise to ova or sperms, the
duplication will be passed to the offspring, if a mutation occurs in one gene, the other one will still be
able to perform its function.
Rakic discovered that the ultimate size of the brain is determined by the size of ventricular zone; each
symmetrical division doubles the number of progenitor cells and thus doubles the size of the brain. The
stage of symmetrical division occurs 2 days longer, and only of few series of progenitor cells can occur
for the large differences in brain size. The period of asymmetrical division lasts longer – this accounts for
the fact that the cortex of humans is 15% thicker.
The genetic processes that accounts for our large brains are just beginning to be discovered. It has been
found that β-catenin is involved in regulation of cell division and tissue growth. It also plays a role in
regulating the size of the cerebral cortex by controlling symmetrical division of progenitor cells. (Chenn
and Walsh: genetic engineering method that resulted in higher levels of the protein, which lead to an
increased the number of progenitor cells, and the size of the mice’s brains increased dramatically;
inversely interfering with the protein causes a decreased size of the brains)
The forebrain
The forebrain: surrounds the rostral end of the neural tube; includes the telencephalon and the
diencephalon.
Telencephalon: includes the cerebral hemispheres that make up the cerebrum, which are covered by
the cerebral cortex and contain the limbic system and the basal ganglia. Both the latter structures are
contained in the subcortical regions located deep, beneath the cerebral cortex
Cerebral cortex: highly convoluted; these convolutions consist of sulci (small grooves), fissures (large
grooves), and gyri (bulges between adjacent sulci or fissures) and greatly enlarge the surface area of the
cortex (2/3 of the surface of the cortex is in the grooves). Its grayish cortex arises because of a
predominance of cell bodies; it is referred to as grey matter. Beneath it there is a large amount of axons
covered in myelin which gives it its name: white matter.
It contains 3 areas which receives sensory input. The primary visual cortex: a region of the occipital lobe
whose primary input is from the visual system. Calcarine fissure: a fissure located in the occipital lobe
on the medial surface of the brain; most of the primary visual cortex is located.
The primary auditory cortex: receives auditory information, is located on the lower surface of a deep
fissure in the side of the brain: the lateral fissure.
The primary somatosensory cortex: a vertical strip of cortex just caudal to the central sulcus receives
information from different regions of the body. Its base and a portion of the insular cortex receive
information concerning taste.
With exception of olfaction is gestation, sensory information is sent to the contralateral hemisphere if
the brain.
Primary motor cortex: region of the cortex that is directly involved in the control of movement. Neurons
of this region are contraleterally connected to muscles of different part of the body.
The rest of the cortex accomplishes what is done between sensation and actions: perceiving, learning,
remembering, planning and acting. These tasks are done in the association areas. The rostral region (to
the central sulcus) is involved in movement-related activities such as planning and executing behaviors
and the caudal region in involved in perceiving and learning.
The cortex contains 4 lobes: frontal, parietal, temporal and occipital
Sensory association cortex: those regions of the cerebral cortex that receive information from the
regions of the primary sensory cortex. Information from the sense is analyzed, perception arises, and
memories are stored there. The regions closest to a primary sensory area receive information from that
area only.
The frontal association cortex is involved in planning and executing movement.
Motor association cortex: in the frontal lobe, rostral to the primary motor cortex, which it controls,
controlling behavior
Prefrontal cortex: the region of the frontal lobe rostral to the motor association cortex, which is more
involved in formulating plans and strategies
Some functions are lateralizing; located primarily on one side of the brain. The left hemisphere
participates in the analysis of information; it is good at recognizing serial events, and controlling
sequences of behavior. The serial functions performed consist of verbal activities; talking, understanding
the speech of other people, reading and writing. The right hemisphere is good at putting isolated
elements together to perceive a thing as a whole.
Corpus callosum: a large bundle of axons that interconnects corresponding regions of the association
cortex on each side of the brain. Most of the connections are symmetrical, but a few of them are not.
This structure is responsible for the unity of our brain, thus out thoughts.
Neocortex: the phylogenetically newest cortex, including the primary sensory, primary motor and
association cortex.
Limbic cortex: located at the medial edge of the cerebral hemispheres; part of the limbic system.
Cingulate gyrus: a strip of limbic cortex lying along the lateral walls of the groove separating the
hemispheres; just above the corpus callosum
The limbic system (forebrain)
MacLean notices that the development of this system coincided with the development of emotional
responses. The amygdala and some other parts of the limbic system are directly involved in emotion
Limbic system: a group of brain regions including the thalamic nuclei, amygdala, hippocampus, limbic
cortex, and parts of the hypothalamus, as well as their interconnecting fiber bundles.
Amygdala: an almond shaped structure in the temporal lobe. It lies anterior and ventral to the
hippocampus. It is made up of several nuclei.
Fornix: a fiber bundle that connects the hippocampus with other parts of the brain, including the
mammillary bodies of the hypothalamus
Mammillary bodies: a protrusion of the bottom of the brain at the posterior end of the hypothalamic
nuclei
Hippocampus: part of the temporal lobe. It is made up of the cornu ammonis fields (CA1-CA4)
Septum: a midline nucleus attached to the corpus callosum and the fornix. It is connected to the
amygdala and hippocampus.
The forebrain: basal ganglia
Basal ganglia: a group of subcortical nuclei in the telencephalon, the caudate nucleus, the globules
pallidus, and the putamen; important parts of the motor system. Parkinson’s disease is caused by a
degeneration of certain neurons located in the midbrain that send axons to the caudate nucleus and
putamen.
The putamen is a band of axons located in the center of the caudate. Together, the caudate and
putamen have a striped appearance and are known together is the striatum
The caudate nucleus: located in the center of the brain. It resembles a C shape with a wide head in the
front tapering to a body and tail at the end.
The globus palliadus: a spherical shaped structure that receives input from the caudate and putamen.
The forebrain: thalamus and hypothalamus (located in the diencephalon)
Thalamus: the largest portion of the diencephalon, located above the hypothalamus; contains
information that project information to specific regions of the cerebral cortex and receives information
from it. It has 2 lobes connected by a bride of gray matter called the massa intermedia, which pierces
the middle of the 3rd ventricle. It is absent in the brains of many people.
Most neural input from the cortex is received from the thalamus.
Projection fibers: an axon of a neuron in one region of the brain whose terminals form synapses with
neurons in another region.
The thalamus is divided into several nuclei. Some are sensory relay nuclei; they receive sensory signals
and relay them to different regions of the cerebral cortex. For example, the lateral geniculate nuclei of
the thalamus receive information from the eye and send axons to the primary visual cortex, and the
medial geniculate nucleus receives information from the inner ear and sends axons to the primary
auditory cortex. The ventrolateral nucleus receives inputs from the cerebellum and sends axons to the
primary motor cortex.
The hypothalamus:
A group of nuclei of the diaencephalon situated beneath the thalamus; involved in regulation of the
autonomic nervous system, control of the anterior and posterior pituitary glands, and integration of
species-typical behaviors (fighting, feeding, fleeing, and mating). It is attached to the thalamus by the
pituitary stalk.
In front of the pituitary is the optic chiasm, an x-shaped connection between the optic nerves, located
below the base of the brain, just anterior to the pituitary gland. The hypothalamic hormones are
secreted by specialized neurons called the neurosecretory cells located near the base of the pituitary
stalk. These hormones stimulate the pituitary gland to secrete its hormones.
The hormones that control the posterior pituitary gland are produced by neurons in the hypothalamus
whose axons travel down the pituitary stalk and terminate in the posterior pituitary. They are carried
through vesicles through the axoplasm of these neurons and collect in the terminal buttons of the
posterior pituitary.
The midbrain (mesencephalon)
A region of the brain that surrounds the cerebral aqueduct – includes the tectum and the tegmentum.
Tectum: the dorsal part of the midbrain; includes the superior colleculi (protrusions on top of the
midbrain; part of the visual system) and the inferior colleculi (protrusions on top of the midbrain; part
of the auditory system), which appears as 4 bumps on the dorsal surface of the brain stem (the stem of
the brain, from the medulla to the midbrain, excluding the cerebellum)
Tegmentum: the ventral part of the midbrain; includes several nuclei controlling eye movement, the
periaqueductal gray matter, reticular formation, red nucleus, and substantia migra
Reticular formation: a large network of neural tissue located in the central region of the brain stem,
from the medulla to the diencephalon. It receives sensory information by means of various pathways
and projects axons to the cerebral cortex, thalamus, and spinal cord. It plays a role in sleep arousal,
attention, muscle tonus, movement and various vital reflexes.
Periaqueductal gray matter: the region of the mid-brain surrounding the cerebral aqueduct; contains
neural circuits involved in species-typical behaviors (fighting and mating). Morphine can decrease an
organ’s sensitivity to pain by stimulating receptors of this region.
Red nucleus: a large nucleus of the midbrain that receives inputs from the cerebellum and motor cortex
and sends axons to motor neurons in the spinal cord.
Substancia nigra: a darkly stained region of the tegmentum that contains neurons which communicate
with the caudate nucleus and putamen in the basal ganglia.
The hindbrain (metencephalon and myelencephalon)
Metencephalon: consist of the pons and the cerebellum
Cerebellum: contains the 2 cereberal hemispheres, covered with the cerebral cortex; an important part
of the motor system. It has a set of deep cerebellar nuclei located within the cerebellar hemispheres
which receives projections from the cerebellar cortex and sends projections out of the cerebellum to
other parts of the brain.
Each hemisphere of the cerebellum is attached to the dorsal surface of the pons by bundles of axons;
the superior, middle, and inferior cerebellar peduncles.
Damage to the cerebellum impairs standing, walking or performance of coordinated movements. It
received information from the visual, auditory, vestibular, and somatosensory cortex. It also receives
information about each individual muscle movements directed by the brain. It smoothes out movement.
Pons: located in the myelencephalon, it contains a portion of the reticular formation, including some
nuclei that appear to be important in sleep and arousal. It also contains a large nucleus that relays
information from the cerebral cortex to the cerebellum.
Myelencephalon: contains the medulla oblongata which contains a part of the reticular formation,
including nuclei that control vital functions such as regulation of the cardiovascular system, respiration
and skeletal muscle tonus.
Chapter 4: psychopharmacology
Psychopharmacology: the study of the effects of drugs on the nervous system and behavior. It has
allowed for the development of drugs and provided tools that enabled the study of the functions of cells
in the nervous system and the behaviors controlled by particular neural circuits.
Drug refers to an exogenous chemical that significantly alters the function of certain cells when taken is
relatively low doses. A drug’s effects are changes that can be observed in an animal’s physiological
processes and behavior. The site of action of a drug is the site where it interacts.
Principles of psychopharmacology
Pharmacokinetics: the process by which drugs are absorbed, distributed within the body, metabolized,
and excreted.
Routes of drug administration
For animals, the most common route is injection, whereas in humans, it is oral administration. The seep
at which the drug is absorbed depends on the time it needs to reach the plasma.
Intravenous (IV) injection: fastest method, but requires care since it enters the bloodstream directly.
Intraperitoneal (IP) injection: in the abdominal wall (peritoneal cavitity ) - good for small lab animals
Intramuscular (IM) injection: into large muscle
Subcutaneous (SC) injection: into the space between the skin, useful only in small amounts.
Oral administration: by mouth, difficult to give to animals, some drugs can’t be taken orally.
Sublingual administration: under the tongue. (nitroglycerine)
Intrarectal administration: for upset stomach
Inhalation: by smoking, treatment of lung diseases
Topical administration: through the skin (hormones). Mucus membrane of the nasal passage can be
used. (insufflation)
Intracerebral administration: for drugs that can’t pass the blood-brain barrier. When a drug is injected in
the ventricle its name is intracerebroventricular (ICV) administration, seldom in humans.
Distribution of drugs within the body
Lipid solubility: the blood brain barrier blocks only for water molecules to pass through. Molecules that
are soluble in lipids pass through the cells that line the capillaries of the CNS, and they rapidly distribute
themselves through the brain. Thus the more lipid-soluble a substance is, the faster it will reach the
brain. (Heroin is faster and more intense than morphine).
Depot binding: binding of a drug with various tissues of the body or with proteins in the blood. As long
as drug molecules are bound to a depot, they can’t reach their site of action. Albumin: source of such
binding; protein found in the blood that serves to transport free fatty acids and can bind with some
lipid-soluble drugs. Depot binding can both prolong and delay the action of a drug. Other sources of
depot binding include fat tissue, bones, muscles, and the liver. (thiopental, anesthetic for the brain, can
bind to muscles and fat tissue)
Inactivation and excretion
Many drugs are deactivated by enzymes, and all are excreted, primarily by the kidneys. The liver plays
an important role in enzymatic deactivation, but some of those enzymes are also found in the blood and
the brain. Sometimes the drug is transformed into another active substance.
Drug effectiveness
Dose-response curve: a graph of the magnitude of the effects of a drug as a function of the
administered amount (mg drug/ kg subject’s body weight). It is obtained by giving subjects various doses
of drugs according to their body weight. Higher doses will cause larger effects until the point of
maximum effect. Most drugs have more than one effect. Morphine is a good example: it has an
analgesic effect and a respiratory depressant. 2 response curves are plotted for this drug and the
difference between these curves are the drug’s margin of safety. The most desirable drugs have a large
margin of safety.
Therapeutic index: the ratio between the dose that produce the desired effect in 50% of the animals
and the dose that produce toxic effects in 50% of the animals. (toxic/desired). The lower the therapeutic
index, the more care must be taken (barbiturates: 3, valium 100+)
Drug effectiveness (depends on site of action and affinity)
Site of action: even if drugs may have the same behavioral effects, they may have different sites of
actions (aspirin stops the pain signal from going to the prostaglandins whereas morphine affects the
activity of neurons in the spinal cord and the brain that are involved in pain perception)
Affinity: the readiness with which 2 molecules join together. Drugs have various affinities for their site
of action; even if 2 drugs have the same binding site, their affinity for it can vary.
Effects of repeated administration
Tolerance: a decrease in the effectiveness of a drug that is administered repeatedly. It is the attempt of
the body to compensate from the effects of a drug; compensatory mechanisms will produce the
opposite reaction. Effectiveness of the binding can be decreased; the receptor become less sensitive or
decrease in number. The second process involved coupling of the receptors with ion channels; one or
more steps in the coupling process become less effective. Once tolerance is established, withdrawal
symptoms (the opposite effects of the drug) will occur.
Sensitization: repeated dose of a drug produce larger and larger effects. It is less common than
tolerance.
Some drugs effects can trigger both tolerance and sensitization (barbiturates and cocaine)
Placebo effects
Placebo: an inert substance given which has no physiological effects given instead of an active drug;
used to control for the effects of mere administration of a drug. If a person thinks that a placebo will
have an effect, it is likely to produce that effect.
Sites of drug action
drugs affecting synaptic connection
antagonist: drug that blocks or inhibits the postsynaptic effects
agonist: drug that facilitates the postsynaptic effects
Effects on production of neurotransmitters: if a drug deactivates one of the enzymes needed for the
synthesis of the neurotransmitter it acts as antagonist, if a drug increases the concentration of one of
the precursor, it is an agonist.
Effects on storage and release of neurotransmitters
The storage of neurotransmitters is done by the same kind of transporter molecules, located in the
membrane of synaptic vesicles that are responsible for reuptake of the neurotransmitter in the terminal
button. Their action is to pump molecules of the neurotransmitter in the membrane, filling the vesicles.
Some of those transporters can be blocked by a drug. Because the vesicles remain empty, nothing is
produced; the drug acts as an antagonist.
Other drugs act as antagonist by preventing the release of neurotransmitter from the terminal buttons.
They do so by deactivating the proteins that cause docked synaptic vesicles to fuse with the presynaptic
membrane. Other drugs do the opposite; they act as agonists by binding with these proteins and
triggering the release.
Effects on receptors
COMPETITIVE POSTSYNAPTIC BINDING
Direct agonist: molecules of the drug that attach to the binding site to which the neurotransmitter
normally attaches; it causes ion channels controlled by the receptor to open, producing postsynaptic
potentials by ion flow
Direct antagonist (receptor blocker): drug that bind to the receptor, occupying the receptor’s binding
site, they prevent the neurotransmitter from opening the ion channel.
NON-COMPETITIVE POSTSYNAPTIC BINDING
Non-competitive: binding of a drug to the site of a receptor; doesn’t interfere with the binding of the
principle ligand
Indirect antagonist: drug that attaches to one of these alternative sites and prevents the ion channels
from opening.
Direct agonist: drug that attaches to one of the alternative sites and facilitates to opening of the ion
channels.
When the autoreceptors of the presynaptic membranes are activated by a drug, the drug acts as an
antagonist; drugs that block them increase the amount of neurotransmitter released.
Presynatpic heteroreceptors: a receptor located in the membrane of a terminal button that receives
input from another terminal button by means of an axoaxonic synapse; binds with the neurotransmitter
released by the presynaptic terminal buttons. Drugs can block or facilitate presynaptic inhibition or
facilitation, depending on whether they block or activate presynaptic heterorecptors
The neurotransmitters released by the dendrites which stimulate autoreceptors located on the same
dendrite, which decrease neural firing by hyperpolarization. This mechanism has a regulatory effect,
preventing these neurons from becoming too active. Drugs that bind with and activate autoreceptors
act as antagonists.
Effects on reuptake and destruction of neurotransmitters
Molecules of neurotransmitters can be taken back into the terminal button through reuptake, or they
are destroyed by an enzyme. Molecules of drug can bind to the transporter molecules responsible for
reuptake and inactivate them, blocking reuptake. They can also bind with the enzyme that destroys the
neurotransmitters and prevent the enzymes from working.
To summarize a drug that activates post-synaptic receptors act as an agonist, and a drug that activates
presynaptic or dendritic autorecptors act as antagonist.
Neurotransmitters and neuromodulators
In the brain the 2 principal neurotransmitters are: GABA (inhibitory) and glutamate (excitatory). Most of
the activity of local neurons involves a balance between these 2 molecules; that account for most of the
information transmitter in the brain. With the exception of pain-detecting neurons, all sensory organs
transmit information to the brain through axons whose terminal buttons release glutamate.
Other neurotransmitters have modulating effect rather than information-transmitting effects; they tend
to activate or inhibit entire circuits of neurons that are involved in entire circuits of neurons.
Acetylcholine
Primary neurotransmitter secreted by efferent neurons if the PNS. All muscular movement is
accomplished by its release. It is also found in the ganglia of the autonomic nervous system and at the
target organs of the parasympathetic branch of the ANS. The axons and terminal buttons of
acetylcholinergic neurons are distributed widely throughout the brain. Its effects are usually facilitatory.
Those located in the dorsal pons play a role in REM sleep. Those located in the basal forebrain are
involved in activating the cerebral cortex, and facilitating learning (perceptual). Those in the medial
septum control the electrical rhythms of the hippocampus and modulate its functions, which includes
the formation of particular kinds of memories.
Botulinum toxin (inhibits) and black widow spider venom affect the release of Ach (stimulates).
Botulinum causes double vision because the muscles moving the eyes are disturbed.
Choline is returned to the terminal buttons by reuptake and converted back to Ach with 50% efficiency.
Hemicholinum can block the reuptake of choline thus it is an ACh inhibitor.
Drugs that deactivate AChE can be used as insecticides and medically; to treat myasthemia gravis by the
use of nestigmine (doesn’t cross the blood-brain barrier)
Nicotinic receptor: an ionotropic receptor that is stimulated by nicotine and blocked by curare (muscle
relaxant used in surgery). Some are found in the axoaxonic synapses where they produce presynaptic
facilitation. Activation of these receptors is responsible for the nicotine addiction.
Muscarinic receptor: a metabotropic receptor that is stimulated by muscarine and blocked by atropine
(one of the belladonna alkaloids which dilate the pupils). They control ion channels through the
production of a second messenger; their action is slower and more prolonged than those of nicotinic
receptors.
Monoamines
Catecholamine: a class of amines that includes dopamine, norepinephrine, epinephrine
Idolamine: a class of amines that includes serotonin
Most of the monoamines are produced by several systems of neurons; most of which are a relatively
small number of cell bodies located in the brain steam, whose axons branch repeatedly and give rise to
an enormous amount of terminal buttons in the brain.
Dopamine (DA)
It can be excitatory or inhibitory depending on the type of postsynaptic receptors. It is implicated in
movement, attention, learning, and reinforcement of the effects of addictive drugs.
Nigrostriatal system: a system of neurons originating in the substantia nigra and terminating in the
neostriatum (caudate nucleus and putamen; control of movement)
Mesolimbic system: a system of dopaminergic neurons originating in the ventral tegmental area and
terminating in the nucleus accumbens (reward), amygdala and hippocampus.
Mesocortical system: a system of dopaminergic neurons originating in the ventral tegmental area and
terminating in the prefrontal cortex (short-term memories, planning, strategy preparation for problemsolving)
Parkinson’s disease: a neurological disorder characterized by tremors, rigidity of the limbs, poor
balance, and difficulty of initiating movements; caused by the degeneration of the neurons connecting
the substantia nigra with the caudate nucleus.
Melanin is produced by the breakdown of dopamine and gives its black coloration to the substantia
nigra. In a deceased person with Parkinson’s this region is rather pale. People with the disease are given
L-DOPA, which can cross the blood-brain barrier. Once it reaches the brain; it is taken up by
dopaminergic neurons and is converted to dopamine; which causes more dopamine to be released and
an alleviation of the symptoms.
AMPT is a drug that acts as an catecholamine antagonist by inactivating the enzyme that converts LDOPA to dopamine. Reserpine prevents the storage of monamines in the synaptic vesicles by blocking
their transporter; no neurotransmitter is released.
Types of dopamine receptors (all metabotropic)
D1 receptors: found exclusively in postsynaptic receptors. Increases the production of the second
messemger, cAMP
D2 receptors: found on both post and presynatpic receptors; decreases the production of cAMP. Same
for the least common D3 and D4 receptors.
Autoreceptors are found in the dendrites, soma, and terminal buttons of dopaminergic neurons.
Activation of those in the dendritic and somatic membrane decreases neural firing by producing
hyperpolarizations. Those located in the terminal buttons decrease the production of dopamine.
Dopamine autoreceptors resembles D2 receptors.
Apomorphine: a drug that blocks dopamine autoreceptors at low doses; at higher doses they block
postsynaptic receptors as well
Amphetamines: causes the release of DA and NE by causing their transporters to run in reverse;
propelling them in the synaptic cleft, and inhibition their reuptake
Cocaine and methylphenidate: block dopamine reuptake. Cocaine blocks also voltage-dependent
sodium ion channels and can be used as a topical anesthetic. Methylphenidate (Ritalin) is used to treat
children with ADHD
Monoamine oxidase (MAO): controls the production of catecholamines. It is found in monoaminerguc
terminal buttons where it destroys excess of catecholamines. Deprenyl destroys MAO-B, which prevents
the breakdown of dopamine, thus acting as an agonist. MAO is also found in the blood where it is
responsible for the breakdown of amines present in foods (chocolate, and cheese) , which could cause
high blood pressure
Choloropromazine: a drug that reduces the symptoms of schizophrenia by blocking dopamine D2
receptors. It is speculated that the disease is caused by an overactivity of dopaminergic neurons
Norepinephrine (NE)
Found in the autonomic nervous system
Epinephrine (adrenaline): a hormone produced by the adrenal medulla, the central core of the adrenal
glands. It also serves as a neurotransmitter in the brain, but is of minor importance compared to NE
AMPT blocks the production of NE and DA
For NE, the final step of synthesis occurs within the vesicles, where dopamine is produced first and then
converted into NE by the action of beta-hydroxylase. Fusaric acid inhibits the activity of this enzymes,
thus the production of NE. Excess NE is destroyed by MAO-A and moclobemine blocks it.
Almost every region in the brain receives input from the noradrenergic neurons, whose cell bodies are
located within 7 regions of the pons and medulla and one region of the thalamus. The cell body of the
most important noradrenergic system begins in the locus coerulus, a nucleus located in the dorsal pons.
Activation of these neurons results in increased vigilance and attentiveness to events of the
environment.
Most neurons releasing NE do so by axonal varicosities, an enlarged region along the length of an axon
that contains synaptic vesicles, and release a neurotransmitter and neuromodulator.
Types of receptors (adrenergic and noradrenergic)
Neurons in the CNS contain B1 and B2 adrenergic receptors, and A1 and A2 adrenergic receptors. Those
receptors are also found in other organs, and are responsible for the effects of epinephrine and NE. In
the brain all receptors are of the A type.
All adrenergic receptors are metabotropic, coupled to G proteins that control the production of a
secondary messenger. They can produce both excitatory and inhibitory effects. In general, the
behavioral response of NE release is excitatory. A1 produces slow depolarization, while A2 produces
slow hyperpolarization. Both Bs increase the responsiveness of postsynaptic neurons to its excitatory
inputs. A2 receptors are also involved in the control of sexual behavior and appetite.
Serotonin (5-HT)
Plays a role in the regulation of mood; in the control of eating, sleeping, and arousal; and in the
regulation of pain. They are also somehow involved in the control of dreams. Its precursor is the amino
acid tryptophan.
PCPA acts as a serotonin antagonist by blocking an enzymes involved in its synthesis.
The cell bodies of serotonergic neurons are found in 9 clusters, which are located in the raphe nuclei of
the midbrain, pons and medulla. It is released by varicosities rather than terminal buttons. The 2 most
important cell bodies are found in the dorsal and medial raphe nuclei. Both the dorsal and medial raphe
nuclei project axons to the cortex and the dorsal raphe innervate the basal ganglia and those in the
medial raphe innervate the dentate gyrus, a part of the hippocampal formation.
At least 9 receptors were indentified, all of which are metabotropic, except for 5-HT3, which is
ionotropic (it controls a chloride channel, which means that it produces inhibitory post-synaptic
potentials). They play a role in nausea and vomiting, because 5-HT3 antagonists are useful to treat the
side effects of cancer medication.
Drugs that inhibit the reuptake of serotonin are very good at treating mental disorders. Fluoxetin
(Prozac) treats depression, some form of anxiety disorder and OCD
Fenfluramine: causes the release of serotonin and blocks its reuptake; used to suppress appetite in the
treatment of obesity.
LSD: a drug that stimulates 5-HT 2A receptors and causes hallucinations.
MDMA: a drug that serves as an noradrenergic and serotonergic agonist; also known as ecstasy; has
excitatory and hallucinogenic effects. It works by reversing 5-HT and NE receptors, and can cause
permanent damage on serotonergic neurons, causing cognitive deficits.
Amino acids
it is difficult to prove that a certain amino acid is a neurotransmitters, since they are used widely by the
body as building blocks of proteins. It is suspected that at least 8 aa are neurotransmitters in the
mammalian CNS
Glutamate
Besides producing postsynaptic potentials, they also have direct excitatory effects (glutamic acid) and
inhibitory effects (GABA) on axons; they raise or lower the threshold of excitation, thus affecting the
rate at which action potential occurs. They have a general modulating role.
Glutamate is the primary excitatory neurotransmitter in the brain and spinal cord. It is produced in
abundance by the cell’s mechanisms, and there is no way of preventing its synthesis without disruption
the cell’s activity.
Glutamate receptors
NMDA: ionotropic glutamate receptor (voltage and neurotransmitter dependent ion channel) that
controls a calcium channel that is normally blocked by magnesium ions that are displaced when the
membrane is partially depolarised.
It contains at least 6 different binding sites; 4 on the exterior of the receptor and 2 located deep within
the ion channel. When opened, the ion channel permits the entry of calcium and sodium, which causes a
depolarization.
Calcium serves as a second messenger, binding and activating various enzymes, which have effects on
biochemical and structural properties of the cell. AP5 blocks the glutamate binding site and impairs
synaptic plasticity and certain forms of learning. For glutamate to bind, glycine must be attached on its
site.
When zinc binds, the activity of the receptor decreases, but if polyamine attaches, its activity is
facilitated. The PCP site binds with an hallucinatory drug, PCP, which serves as an indirect antagonist
since calcium ions can’t pass through. Alcohol acts as a NMDA antagonist
AMPA: an ionotropic receptor that controls a sodium channels; stimulated by AMPA. It is the most
common. When glutamate attaches to the binding site, it produces EPSPs
Kainite: ionotropic receptor that controls a sodium channel; stimulated by kainic acid
Metabotronic glutamate receptor: there appears to be 8 subtypes, little is known except that some
serve as presynaptic autoreceptors
GABA (produced by glutamic acid)
Allylglycine: a dug that inhibits the activity of GAD and blocks the synthesis of GABA
It is an inhibitory neurotransmitter, and appears to have a widespread activity throughout the brain and
spinal cord. Without its effects, seizures would occur
GABAa receptor is ionotropic and controls a chloride channel. They have 5 binding sites, the primary
binging for GABA. Muscimol serves as a direct agonist, and bocuculline blocks this site and acts as a
direct antagonist. A second site binds with tranquilizing drugs, benzodiazepine (Valium) and
chloradiazepine (Librium). The 3rd site binds with barbiturates, and the 4th site binds with various
steroids. The 5th site binds with picrotoxin, which inhibits the activity of GABA. Alcohol binds with one of
these sites. Their natural ligands have not yet been identified.
GABAb receptor is metabotropic and controls a potassium channel. Coupled to a G protein, it serves as
both as postsynaptic receptor and a presynaptic autoreceptor. Baclofen serve as an agonist. Their
activity stimulates potassium channels, producing hyperpolarizing inhibitory postsynaptic potentials.
Glycine
It is an Inhibitory neurotransmitter in the spinal cord and lower portions of the brain.
The bacteria that causes tetanus releases a chemical that prevents the release of glycine, which causes
the muscles to contract continuously
The glycine receptor is ionotropic and controls a chlorine channel; when active, it produces an inhibitory
post-synaptic potential. Strychnine serves as an antagonist.
Some terminal buttons in the brain release both GABA and glycine. The advantage for the corelease of
these 2 chemicals is that they produce long-lasting postsynaptic potentials. The glycine stimulates rapid
ionotropic receptors, and the GABA stimulates long-lasting metabotropic receptors.
Chapter 5: methods and strategies of research
Experimental ablation
Experimental ablation: the removal or destruction of a portion of the brain in laboratory animal;
presumably, the functions that can no longer be produced are the ones the region previously controlled.
Evaluating the behavioral effects of brain damage
Lesion studies: synonym for experimental ablation
Its goal is to study what functions are performed by different regions of the brain and how these
functions are organized to produce complex behavior. Neural circuits in the brain functions, which
contribute to the performance of a behavior.
The fact that all brain regions are interconnected complicate this type of study
Producing brain lesions
Excitotoxic lesions: an excitatory amino acid is injected into the target of the brain. The chemical
destroys cell bodies by stimulating them to death. This method is highly selective; it destroys cell bodies
only, leaving the axons of neurons that pass nearby intact. It can create selective neurochemical lesions
thereby depleting dopamine, serotonin, NE and ACh in specific brain regions.
Aspiration lesions: the brain area of interest is removed by suction using a fine-tipped hand-held glass
pipette. It can damage underlying white matter and major blood vessels. It is a non-selective method
because it removes cell bodies and fibers of passage.
Radio-frequency lesions: small subcortical lesions are made by passing a radiofrequency through a
stainless steel wire that is insulated except the tip. The wire is guided stereotaxically. The electric
current produces heat that destroys the cells in the region surrounding the tip of the wire. The size and
shape of the lesion can be determined by the duration and intensity of the current.
Antibody lesions: a toxic chemical is attached to antibodies that will bind a particular type of proteins
found only on certain types of neurons in the brain. The antibodies target these proteins, and the
chemical kills to cells to which the proteins are attached.
Sham lesions (operated control): for experimental purposes, a group of animals will undergo the same
experimental procedure without the excitotoxin, frequency or aspiration.
Most lesions are permanent. Temporary lesions can be made by infusing a local anesthetic (lidocaine)
which blocks action potential for 10mins, or infusing a GABA agonist (muscimol) which is an inhibitory
neurotransmitter.
Stereotaxic surgery
This apparatus allows for the different types of lesions studies to be performed.
Stereotaxic atlas: a collection of drawings of sections of the brain of a particular animal with
measurements that provide coordinates for surgery. The reference point is often the bregma, the
junction between the sagittal and coronal sutures of the skull. The junction at which the structures meet
at the back of the head is called lambda. Because the structures can vary a bit, the atlas only provides an
approximate location.
Histological methods
After producing a lesion and observing its effects on the animal’s behaviour, the brain must be sliced,
and stained so that it can be observed under a microscope to see the site of the lesion. They also allow
locating structures and seeing how they are connected.
In order to prevent decay, a fixative (formalin) must be used. Then perfusion is done to remove the
blood and replace it with another fluid. Slicing is done with a microtome, an instrument that produces
very small slices (10 to 80 um, those for the electron are 1um). Slices are referred to as sections.
Nissl stains: methylene blue dye the stains the cell bodies of brain tissue. The material that takes up the
dye consists of RNA, DNA and associated proteins located in the nucleus, and scattered in the form of
granule in the cytoplasm. Cresyl violet is most commonly used. The dark regions represent cell bodies
and the light regions, axons and bundles of fibre, which don’t take up the dye.
Golgi stains: allows us to visually identify the external structure of neurons, whose silhouettes are
revealed in great detail but the internal structure of the cells is invisible.
The electron microscope
Transmission electron microscope: a microscope that passes a focused beam of electrons through thin
slices of tissue to reveal extremely small details (organelles) x 1 000 000
Scanning electron microscope: provides 3D information about the shape of the surface of a small object
by scanning it with a beam of electrons. Less precise.
Confocal laser scanning microscope: a microscope that provides high-resolution images of various
depths of thick tissue that contains fluorescent molecules by scanning the tissue with light from a laser
beam. Allows for living tissue to be scanned.
Tracing neural connections
Neurons in the VMH appear to play a role in functions required for copulatory behavior in female rats.
Its connections with the rest of the brain must be assessed before conclusions can be made.
Tracing efferent axons (anterograde labeling methods)
Chemicals that are taken up by dendrites or cell bodies and are then transported through the axons
toward the terminal button are used when tracing the paths of axons projecting away from cell bodies.
PHA-L, a drug derived from kidney beans, is injected in the regions of interest. The drug is taken up by
dendrites and is transported through the soma to the axons, where they travel by means of fast
axoplasmic transport to the terminal buttons. Within a few days, the cells are filled with it, the animals is
savagely slain and studied
Immonocytochemical method: a histological method that uses radioactive antibodies or antibodies
bound with a dye molecule to indicate the presence of particular proteins or peptides. The antibodies
attach themselves to the antigens.
Tracing afferent axons (retrograde labeling)
Used when tracing a path of axons projecting toward a particular region of the brain. Chemicals that are
taken up by terminal buttons and carried back through the axons towards the cell bodies are injected
into the brain region of interest (fluorogold whose molecules fluoresce under light)
The anterograde and retrograde methods that were described can only trace a single link in a chain of
neurons. Transneuronal tracing methods uses a pseudorabies virus for retrograde tracing and herpes
simplex virus for anterograde virus. Such viruses are injected into a brain region, infect it, and spread
throughout the infected neurons and are eventually released, passing on the infection to other neurons
that form synaptic connections with them. The longer the virus is left, the larger amount of neurons it
will infect.
Studying the structure of the living human brain
Studies are done in humans who suffered brain damage, to identify which functions the damaged areas
performed. Such studies are done in healthy individuals of course.
Computed tomography (CT): the first imaging technique which provides detail anatomical data that
revolutionized neurology and experimental neuropsychology. The ring contains an X-ray tube and
directly opposing it, an x-ray detector. When the x-ray beam passes through the patient’s brain, the
amount of radioactivity is measured. A computer translates this input into pictures.
Magnetic resonance imaging (MRI): similar image with greater spatial resolution. It passes extremely
strong magnetic fields through the patient’s head, causing atomic nuclei to spin in a particular direction.
If a radio frequency is then passed, these H nuclei emit radiofrequency of their own.
Diffusion tensor imaging (DTI): uses modified MRI scanners to reveal bundle of myelinated axons in the
living human brain. Molecules of water will align in a direction parallel to the axons that make up the
bundles. The MRI detects the movement of the water molecules. Color is added by the computer.
Recording and stimulating neural activity
Recordings can be made chronically, over an extended period of time after the animal recovers from
surgery, or acutely, during a short period of time while the animal is anesthetised, usually restricted for
sensory pathways.
Recording with microelectrodes (single-unit recording)
The activity of a single neuron over an extended period of time is recorded. The wires are insulated, so
that only their tips are bare. The electrodes are implanted in the brain, which are attached to sockets
that bond to the animal’s skull using dental ciment. Animals pay no attention to them. Devices that
permit movement of the electrodes are implanted. Signals must be amplified.
Recording with macroelectrodes (multiple-unit recording)
An electrode is used to record the activity of a large number of neurons in a particular region of the
brain. Postsynaptic potentials are measured by the electrode (which comes in various shape) that is
attached to an amplifier which records an EEG. Macroelectrodes can be implanted in the human brain
and records are traced by a polygraph. EEGs provide a diagnostic tool with which particular states of
consciousness or types of cerebral atrophy are associated with different patterns of EEG waveform. It
can also be used during surgery.
Magnetoencephalography
As action potentials pass along, magnetic fields are also produced. SQUIDS, superconducting quantum
interference devices can detect these extremely small fields. This procedure detects groups of
synchronously activated neurons by means of the magnetic field. It is performed with
neuromagnetometers, devices that contain an array of SQUIDS. A computer can examine the data.
Recording the brain’s metabolic and synaptic activity
Event-related potential (ERP): electrical signals recorded from the brain that occurs after the onset of a
stimulus. The electrical pattern is represented in waveform. Results must be averaged over many trials
to have an emerging pattern of value. P.36. An experiment suggested that ERP can predict if an event
will be remembered or not, but they aren’t easy to interpret. They need to be supplemented by other
techniques in order to provide a more complete picture of brain activity.
Positron emission tomography (PET): an imaging technique in which a participant is injected with a
radioactive substance, 2-deoxyglucose (2-DG), which will be taken by the cells but not metabolised. This
substance will get absorbed in the blood and circulates to the brain. A scanner is then used to detect the
flow of blood to particular areas of the brain. When a particular function is engaged, activity will result in
the brain areas that are responsible. When the part of the brain is active, it will use more oxygen, which
will require increased blood flow. There are limits to the amount of radiation that can be taken,
therefore a limit to the amount of information obtained, and the radioactive substance decays fast. They
must be produced on site in a particle accelerator called cyclotron. The positrons being emitted from the
person’s brain must be recorded for a long amount of time, missing rapid short-time events occurring.
In animals, once the 2-DG will be absorbed an audioradiography is done. It is a procedure that locates
radioactive substances in a slice of tissue; the radiation exposes a photographic emulsion or a piece of
film that covers the tissue. The radioactive molecules will come up as silver grains. The most active
regions, will show the most radioactivity.
When neurons are active, particular genes in the nucleus call immediate early genes are turned on and
particular proteins are produced, which bind with the chromosomes, and indicates that the neuron has
just been activated. Fos is a protein produced in the nucleus of a neuron in response to synaptic
stimulation.
Functional magnetic resonance imagery (fMRI): a non-radioactive magnetic procedure for detecting the
flow of oxygenated blood to various parts of the brain. The patient’s head is put in a large magnetic
field, which causes atoms in the brain to become aligned with the field. Changes in the blood flow can
be picked up as alterations of the field. It is a BOLD signal, blood oxygen level dependent. They are more
detailed, faster, and have a higher 3D resolution.
Stimulating neural activity
Sometimes, we need to artificially change the activity of specific regions of the brain to see the effects of
these changes on behaviour.
Electrical stimulations: passing an electrical current through a wire inserted into the brain.
Chemical stimulation: injection of a small amount of excitatory amino acid (glutamic kainic acid), which
will stimulate glutamate receptors, thus activating the neuron. An apparatus can be permanently
attached to the animal’s skull. A cannula is placed, and a smaller one is used to inject the chemical. It
activates cell bodies, but not axons.
Through both electrical and chemical stimulation, a large number of neurons will be activated, and
normal behaviour won’t occur. It would be ideal to stimulate precise circuits.
Microiontopheresis: determines the effects of transmitter substances (or drugs) on the activity of
individual neurons. It uses multibarreled micropipettes which discharges small quantities of drug when
an electrical current is passed through the micropipettes. The recording electrode detects the activity of
the cell exposed to the drug.
Photostimulation (optogenetics)
It uses light to artificially stimulate cells. The light activates a light sensitive protein which excites the cell
that expresses that protein.
ChR2 (in green algae), a protein that controls a cation channel which opens when blue light hits,
enabling the influx of cation thereby depolarizing the membrane.
NpHR (in bacterium), a protein that controls an anion transporter, which enables the influx of anions,
when yellow light hits, thereby hyperpolarizing the membrane.
The effects of both proteins begin and end rapidly when the wavelength is turned off. They can be
introduced into neurons by attaching the genes that code for them in the genome of harmless viruses,
which are injected into the brain, where they infect neurons and begin expressing the proteins, which
are inserted into the cell membranes. Genes can be modified so that they will only be expressed in
certain types of neurons.
A small hole can be drilled into the head and LEDs can be attached, optical fibres can also be implanted.
Transcranial magnetic stimulation
Stimulation of the cerebral cortex by means of magnetic fields produced by passing pulses of electricity
through a coil of wire placed next to the skull; interferes with the functions of the brain regions that is
stimulated.
Neurochemical methods
Finding neurons that produce particular neurochemicals
It is possible to localize the chemicals themselves, the enzymes, and the messenger RNA involved in
their synthesis. Peptides can be localized directly by means of immunocytochemical methods. (if it isn’t
possible to trace the neurotransmitter, it is possible to trace the enzyme that produces it)
In situ hybridization: the production of radioactive RNA that is complementary to a particular
messenger RNA in order to detect the presence of the messenger RNA. Audioradiographic methods
would be used to identify the location of the messenger RNA responsible for a particular synthesis.
Localizing particular receptors
Audioradiography can be used in which slices of brain tissue are exposed to a solution containing a
radioactive ligand for a particular receptor. The slices would then be rinsed so that only the radioactive
molecules bound to their ligand would remain. Then audioradiographic methods are used to localize.
Immunocytochemistry methods can also be used during which slices of brain tissues are exposed to
antibodies. The slices are then looked up under a microscope at a particular wavelength.
Measuring chemicals secreted in the brain
Microdialysis: a procedure for analysing chemicals present in the interstitial fluid through a small piece
of tubing made of a semi-permeable membrane that is implanted in the brain. Stereotaxic surgery is
used to implant the probe in the rat’s brain. A small amount of liquid similar to the extracellular fluid is
inserted, it circulates, takes up molecules of the extracellular fluid and is taken up for analysis. The
amount of neurotransmitter released is analysed. (the release of dopamine in the nucleus accumbens
plays an important role in reinforcement)PET scanners can localize any radioactive substances that
emits positrons, thus we benefit from this in human studies.
Genetic methods
It is clear that genes play a role in the difference of behaviour in individual. When there is a genetic
defect, cognitive and behavioural impairments may occur. The influence of heredity is more subtle.
Twin studies: compare the concordance trait between monozygotic twins and dizygotic twins. If the
disease if genetic, the concordance between monozygotic twins should be higher than that of dizygotic.
It has been found that traits and disorders can be genetically inherited.
Adoption studies: comparison between people who were adopted early in life and their biological
parents or non-adopted siblings.
Targeted mutations: mutated gene (knockout gene) produced in the laboratory and introduced into the
chromosome of mice; fails to produce a functional protein. It allows identifying the function of enzymes.
Conditional knockouts also exist, in which the gene ceases to function under particular conditions only.
Antisense oligonucleosides: modified strand of DNA or RNA that binds with a specific molecule mRNA
and prevents it from producing its protein. Once the molecules of mRNA are trapped in this way, they
are destroyed by the enzymes present in the cell.
Chapter 6: vision
Sensory receptors: a specialized neuron that detects a particular stimulus, category of physical event.
Most of them lack axons; a portion of their somatic membrane forms synapses with the dendrites of
other neurons
Sensory transduction: the process by which sensory stimuli are transduced into slow, graded receptor
potentials.
Receptor potential: a slow, graded electrical potential produced by a receptor cell in response to a
physical stimulus. They affect the release of neurotransmitter, and modify the pattern of firing of the
neuron.
Approximately 20% of the cerebral cortex is plays a direct role in the analysis of visual information.
The stimulus
Our eyes can detect electromagnetic radiation with a wavelength between 380 and 760 nm. The
perceived color is determined by 3 dimensions:
1-hue: determined by the dominant wavelength
2-brightness: intensity of the radiation increases and causes an increase of brightness.
3-saturation: relative purity of the light that is being perceived. Colors with different amount of
saturation contains a mixture of different wavelength
Anatomy of the visual system
For vision to occur, an image must be focused on the retina, which causes changes in the electrical
activity of neurons in the retina. These messages will be sent through the optic nerves to the brain.
The eye
The eye is suspended in the orbit, and they are held in place and moved by 6 extraocular muscle
attached to the tough, white outercoat of the eye called the sclera, which doesn’t permit light to enter.
The muscle’s attachments are hidden by the conjunctiva, a mucous membrane that lines the eyelid. The
eye can make 3 possible types of movements:
1-vergence: keep both eyes fixed on the same target
2-saccadic: rapid and jerky, they permit a shift in gaze from one point to another.
3-pursuit: allow us to maintain a moving object.
The cornea, is the outer, transparent front layer of the eye that permits light to enter. The amount of
light that enters is regulated by the pupil, which is an opening in the iris (pigmented ring of muscles).
The lens consists of several transparent layers. The ciliary muscles can change the size of the pupil to
allow the eye to focus, a process known as accommodation. After passing through the lens, light reaches
the vitreous humor, and then falls on the retina.
There is a site called the blind spot, which is the point at which the optic nerve exits at the back of the
eye and has no receptors. It is also called optic disk.
The retina consists of several layers of neuron cell bodies, their axons and dendrites, and the
photoreceptors. Its main layers are: photoreceptive, bipolar cell, and ganglion cell layer. Light must pass
through the overlaying transparent layers to reach the photoreceptors located at the back of the retina.
They then send messages to bipolar and ganglion cells located closer to the back of the eye. The
ganglion cells’ axons loop around each other and travel back to the brain through the optic nerves.
The retina also contains horizontal cells, interconnecting adjacent photoreceptors and the outer
processes of the bipolar cells, and amacrine cells, neurons connecting ganglion cells and the inner
processes of the bipolar cells.
Photoreceptors:
Light sensitive neurons located in the retina. Their function is to transducer light into electrical potential.
called rods (120M) and cones (6M) are located on the retina.
Rods: sensitive to low light, at the periphery of the retina. In the periphery, several receptors converge
onto the bipolar and ganglion cells. The precise location and shape of input is greatly impaired. It allows
the perceptions of faint light. They are monochromatic, and provide poor visual acuity.
Cones: sensitive to bright light, allow color vision. They are located towards the center of the retina. The
fovea, specialized in visual acuity, is at the center of the retina and contains the largest amount of cones.
In the fovea, each cone connects to a single bipolar cell, which in turn connects to a single ganglion cell.
Thus the receptors in the fovea can register the exact location of the input. It is sensitive to details. They
are trichromatic.
The photoreceptors are made up of an outer segment, which contains several hundreds of lamellae
(thin membrane), connected by a cilium to the inner segment, which contains the nucleus, cell body and
axon like process. They provide input to both bipolar and horizontal cells.
Photopigment: molecules located in the membranes of the lamellae, they release energy when struck
by light. There are proteins bound bonded to retinal, a substance derived from vitamin A and are
responsible for transduction of visual information. They are made up of opsin (a protein) and retinal (a
lipid derived from vit A).
Rhodopsin: photopigment of human rods. When exposed to light it breaks down in its components: rod
opsin and retinal. It changes color from pink to pale yellow, thus the light bleaches rod opsin. The
splitting of the photopigment causes a change in the membrane potential of the photoreceptor which
causes it to release glutamate. (the photoreceptors and bipolar cells don’t produce action potentials).
Translation of light into neural signals
The greater the depolarization of their membrane, the more glutamate will be released. The
hyperpolarizing effect of light on the photoreceptor membrane reduces the release of glutamate.
Reduced glutamate depolarizes the bipolar cell. Depolarization of the bipolar cell leads to increased
glutamate release causes the ganglion cells to increase the rate of firing. It is only the ganglion cells that
produce the action potential. Because the neurotransmitter normally hyperpolarize the dendrites of the
bipolar cells by binding with inhibitory alumate receptors, a reduction in its release causes the bipolar
cell to depolarize, causing more neurotransmitter to be released, which depolarize the membrane of the
ganglion cells and raise this cell’s rate of firing. Other ganglion cells can decrease their rate of firing in
response to light (they are connected to bipolar cells that form different kinds of synapses with the
photoreceptors)
In the dark: ion channel in the photoreceptor membrane are normally open. The ion channels admit
cations. The ion channels are held open by molecules of cGMP, a second messenger. The entry of cation
depolarizes the membrane which results in a continuous release of glutamate.
In the light: the rhodopsin molecule will split. The chemical reaction involves a G protein and a
phosphodiesterase enzyme that will destroy the cGMP. This closes the ion channel. Cations can no
longer enter the cell and the membrane hyperpolarizes and the release of glutamate decreases.
Connection between eye and brain
The retina-geniculate striate pathway conduction signals from the retina to the primary visual cortex
(striate cortex or area V1) via the lateral geniculate nucleus (LGN).
The axons of the ganglion cells bring information to the rest of the brain; the ascend trough the optic
nerve and reach the dorsal lateral geniculate (LGN) of the thalamus. The LGN contains 6 major layers of
neurons, each of which receives input from one eye. The magnocellular layers (inner layers) contain
larger cell bodies and receptors then those of the parvocellular layers (4 outer layers). The koniocellular
sublayers contains neurons that receive input from different types of ganglion cells.
The neurons in the LGN send their axons through the optic radiations to the primary visual cortex
(striate cortex; contains dark-staining layer), surrounding the calcarine fissure. The optic nerves join
together at the base of the brain to form an x-shaped optic chiasm where the axons from ganglion cells
serving the inner halves of the retina (nasal sides) cross through the chiasm and ascend to the LGN on
the other side of the brain. The axons from the outer halves of the retina (temporal sides) remain on the
same side of the brain. The lens invert the images projected on the retina; each hemisphere receives
information from the contralateral half of the visual scene.
There are other pathways other than the primary geniculo-cortical pathway that axons can take. A
pathway to the hypothalamus controls activities based on 24hours. A pathway to the optic tectum and
the preteectal nuclei coordinate eye movement, controls the muscles of the iris and the ciliary muscles,
and help pay attention to sudden movement in our periphery.
Coding of visual information in the retina
Coding of light and dark
Receptive field: the portion of the visual field in which the presentation of visual stimuli will produce an
alteration in the rate of firing of a particular neuron. Its location depends on the location of
photoreceptors that provide it with visual information. It is the part of space in which the light must fall
for the neuron to be stimulated.
If a neuron receives information from a photoreceptor in the fovea, its receptive field will be at the
fixation point; if the photoreceptor is in the periphery, its receptive field will be off to one side.
In the periphery, many individual receptors converge on a single ganglion cell, bringing information from
a large part of the retina, hence a large area of the receptive field; whereas the fovea contains an equal
number of cones and ganglion cells.
The find a receptive field, one must shine light in various locations while recording from a neuron. If the
light from a particular spot excites the neuron, that location is part of the neuron’s excitatory receptive
field (ON firing). If the light inhibits activity, the location is in an inhibitory receptive field (OFF firing)
ON and OFF firing
Neurons respond with either ON or OFF firing depending on the location of the receptive field.
Stimulation of the central field and the surrounding field have contrary effects.
ON cells: excited by light falling in the centre, but inhibited by light falling in the surround.
OFF cells: excited by light falling in the surround, but inhibited by light falling in the center.
ON/OFF cells: respond briefly to light, in primates most of them project directly to the superior
colliculus, involved in visual reflexes. Thus they don’t play a direct role in form perception.
It was found that ON and OFF cells signal different kinds of information; when synaptic transmission of
ON cell was inhibited, animals had difficulty seeing bright objects on a darker background, and vision in
dim light is completely blocked. Thus rod bipolar cells must be the ON type.
Seeing edges (the perception of contrast)
Contrast enhancement: the center-surround organization of the ganglion cells receptive fields enhaces
our ability to detect the outline of objects, even when the contrast between the object and the
background is low. These exaggerated borders don’t exist; they are added by our visual system.
Lateral inhibition: when a receptor field fires, it inhibits its neighbours via a lateral neural network; it
spreads laterally across an array of receptors. The amount of lateral inhibition produced by a receptor is
greatest when it is most intensely illuminated, and it has the highest effect on its intermediate
neighbours. The ON cells located in the brighter region but whose surrounds are located at least
partially in the darker region will have an the highest rate of firing.
Coding of color
The frequency perceived by the eye is the wavelength reflected by the object, all others are absorbed by
it.
Cones and photoreceptors are sensitive to different portions of the visible spectrum.
No single neuron can simultaneously signal brightness and color so our perceptions must rely on a
combination of responses by different neurons.
Trichromatic theory of Color Vision (Young-Helmholtz Theory)
Color perception is a function of the relative rates of responses by 3 types of cone photoreceptors, each
sensitive to a different set of wavelength. Any colors can arise from mixing of 3 wavelengths, which are
discriminated by the ration of activity of the 3 types of cones.
Each cone is sensitive to shot (blue), medium (green), and large (red) wavelengths. Controlled by the
particular opsin a photoreceptor contains. Their relative number varies among individuals. Red cones
appeared first, blue cones arose (8% of cones, 1.5% information transmitter to ganglion cells), and finally
a red opsin duplication gave rise to the green cones.
Problems: it can explain why yellow is perceived as a pure color; some colors appear to blend while
others don’t, and even seem to be opposites.
Retinal ganglion cells: opponent-process coding (Hering)
We perceive color in terms of paired opposites; red vs. green, yellow vs. blue, black vs. white (brightness
in the center and surround).
Some neurons are excited by one set and inhibited by another.
The bipolar cell is excited by the blue light, but inhibited by green, yellow, and red. An increase in the
bipolar cell activity leads to a blue experience, but a decrease leads to a yellow experience. Extended
blue light stimulation fatigues to bipolar cell. If a blue light is substituted by white light, bipolar cell
becomes more inhibited and produces a yellow experience.
They can function in center-surround activity; red-green ganglion cells are activated by red and inhibited
by green. A neuron can either increase or decrease its rate of firing; not both at the same time (no
yellow-blue color)
Adaptation: negative after image
The image seen after the portion of the retina is exposed to an intense visual stimulus; consist of colors
complementary to those of the physical stimulus. They cause adaptation in the firing rate of ganglion
cells; when inhibited or activated for a prolonged period of time, can observe a rebound effect.
Complementary colors: colors that make white gray when mixed together.
Color vision deficiency
Protanopia: confuses red and green. The world is seen in shades of yellow and blue
Deuteranopia: confuses red and green. Their green cones are filled with red opsin
Tritanopia: rare, faulty gene not located on the X chromosome; difficulty with shot wavelengths. They
lack blue cones.
Achromatopsia: true color blindness.
Analysis of visual information; role of the striate cortex
Anatomy of the striate cortex: contains a map of the contralateral half of the visual field. 25% is
devoted to analysis of information coming from the fovea. Neurons don’t only respond to light but also
to features of the visual world. They gather information from different sources as to detect features
that are larger than the receptive field of a ganglion cell in the LGN.
Orientation and movement: orientation-sensitive neurons (Hubel and Wiesel 1960)
An orientation sensitive neuron in the striate cortex will respond only when a line of a particular
orientation appears within its receptive field.
Simple cells: an orientation sensitive neuron organized in an opponent fashion (a strand of particular
orientation may excite the cell if placed in the center, and inhibit it if placed at the surround)
Complex cells: neurons which don’t have an inhibitory surround; they respond when line moves
perpendicular to its angle of orientation. They also serve as movement detectors. Equal response to
white line on dark background and dark line on white background.
Hypercomplex cells: neurons that have inhibitory regions at the end (or ends) of a line segment. They
detect the location of ends very well
Spatial frequency and sine wave gratings (DeValois et al., 1978)
Sine wave grating: a set of equally spaced, parallel, alternating light and dark stripes that vary in
brightness, according to a sine-wave function along a lien perpendicular to their lengths. It is designed
by its special frequency (cycles per degree). The visual angle is smaller is the sine-waves are closer
together.
Most neurons in V1 respond to a particular spatial frequency placed in the appropriate part of its
receptive field. Different neurons detect different frequencies,
The response of a cell in the striate cortex (Albrecht) He found that a single cell contains multiple
excitory and inhibitory regions surrounding the center.
High and low spatial frequency
High: sharp edges, details
Low: while the contours of images deficient in high frequency information look fuzzy, they still provide
information, and we can still make out the form.
Retinal disparity
Monocular vision: neurons respond to visual stimulation in one eye.
Binocular vision: neurons respond to visual stimulation in both eyes. Provides perception of depth.
Stereopsis: the perception of depth that emerges from the fusion on 2 slightly different projections of
the image on the 2 retinas. The difference between the 2 eyes’ images, which is a result of the eye’s
horizontal separation is referred to as binocular or retinal disparity.
Color: in V1 information from color-sensitive ganglion cells is transmitter through the LGN to specialized
cells grouped together in cytochrome oxidase (CO) blobs.
Analysis of visual information: role of the association cortex
Visual information received from V1 is analysed in the visual association cortex.
Extrastriate cortex: a layer of neurons that surround the striate cortex. It consists of different regions
that form different maps. Each region respond to a specific feature of the visual environment,
Outputs of V1 are sent to areas of the extrastriate cortex (area V2/V3/MT) in a hierarchial fashion.
What and where visual pathways
Ventral stream: recognizes what the object is and its color; terminates in the inferior temporal cortex.
Respond to the contours of 3D objects.
Dorsal stream: recognizes where the object is and whether it’s moving; terminates in the posterior
parietal cortex. Receives mostly magnocellular input (black and white; motion). Respond to large areas.
Perception of form
The inferior temporal (IT) cortex consists of area TE and area TEO. The analysis of visual information is
hierarchical; the receptive fields of neurons increase in successive regions as the visual image becomes
more complex. The receptive field in TH are larger than those of area TEO. These cells respond to 3D
objects and continue to respond when the image moves to different locations, changes in size, is
partially occluded by other objects etc. Thus cells in IT participate in recognition of objects rather than
analysis of specific features.
Perception of color
Animals: area v4 is responds to a variety of wavelengths. It is involved in the analysis of form and color,
they had an unusually large secondary receptive field. They respond to particular wavelengths but
subtracted out the amount of that wavelength that was present in the background. They serve for color
constancy. TEO is involved in color vision. Golb neurons have sensitivity to color and weak sensitivity to
shape; opposite for interglobs.
Humans: cerebral achromatopsia: inability to discriminate among different hues; caused by damage to
V8.
Perception of form: information sent to area V2 and then to the subregions of the visual association
cortex and constitute the ventral stream.
Animals: recognition of patterns and identification of objects takes place in the inferior temporal cortex,
which consists of TEO and TE. The size of the receptive fields grow as the hierarchy is ascended. Those in
TE are the largest, and respond to 3D objects
Humans: visual agnosia: inhability to recognize objects, persons or shapes in the absence of blindness or
memory loss.
LOC: a region of the extrastriate cortex responsible for the perception of objects other than people’s
faces and bodies.
Patients with propagnosia can’t recognize faces due to damage in the fusiform gyrus.
Extrastriate body area (EBA): a region of the visual association cortex that is responsible for the
perception of human body and body parts other than the face. Overlaps the FFA
Parahippocampal place area (PPA): a region of the limbic cortex on the medial temporal lobe; involved
in the perception of particular places (scenes).
Perception of movement:
Area MT (V5): of the extrastriate cortex contains neurons that respond to motion. It receives input
directly from the striate cortex as well as the superior colliculus which is involved in visual reflexes.
Damage to it leads to akinetopsia; the inability to perceive movement.
Area MST: (V5a) performs further motion analysis such as radial, circular and spiral motions.
Optic flow: the analysis of the relative movement of the visual elements around us. It provides
information about objects in the environment as we move around or as objects move around in relation
to us.
Perception of motion and perception of form
Although motion is processes by MT/MST, the ability to detect form from motion is processes in the
right medial occipital lobe.
Perception of spatial location
Intraparietal sulcus (IPS): the end of the dorsal stream of the visual association cortex; involved in
perception of location, visual attention, and control of eye and hand movements.