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Transcript
Chapter 12: Nervous Tissue
Chapter Outline and Objectives
OVERVIEW OF THE NERVOUS SYSTEM
1. Identify the structures that make up the nervous system.
2. Classify the organs of the nervous system into central and peripheral divisions and their
subdivisions.
3. List and explain the three basic functions of the nervous system and indicate the direction
of afferent and efferent information flow.
HISTOLOGY OF NERVOUS TISSUE
4. List the three parts of a neuron.
5. Describe the structures located in a neuron cell body and their functions.
6. List the names given to collections of cell bodies in the CNS and PNS.
7. Describe the function of the dendrites.
8. Describe the direction of information flow through an axon.
9. List the names given to collections of axons in the CNS and PNS and how they are
bundled together.
10. Identify neurons on the basis of their structural and functional classifications.
11. Contrast the general functions of neuroglia and neurons.
12. Describe the relative number of neuroglia compared to neurons.
13. List the four types of neuroglia in the CNS and describe the function for each.
14. List the two types of neuroglia in the PNS and describe the function for each.
15. Identify the cells that produce myelin, describe how the sheath is formed, and discuss its
function.
16. Define the neurolemma and discuss its function.
17. Describe the Nodes of Ranvier and tell why they are important for axon signal
transmission.
18. Discuss multiple sclerosis in terms of anatomical changes and causes.
19. Describe the difference between gray and white matter, and give examples of each.
ELECTRICAL SIGNALS IN NEURONS
20. Distinguish between action potential and graded potentials.
21. Identify the basic types of ion channels and the stimuli that operate gated ion channels.
22. Describe the ions, channels, and integral-protein pumps that contribute to generation of a
resting membrane potential.
23. Discuss the All or none principal in regards to neurons.
24. Discuss the features of the graded potential including areas where generated, size,
properties, and type.
25. Describe the effect the sum of the excitatory and inhibitory stimuli has on the neuron.
26. List the sequence of events involved in generation of a nerve impulse.
27. Define and give a value for the threshold voltage.
28. Describe the events involved in depolarization of the nerve cell membrane and tell which
charges are located where.
29. Describe the repolarization of the nerve cell membrane and tell which charges are located
where.
30. Define refractory period and describe why it occurs.
31. Discuss how the sodium ion flow in one area of an axon leads to initiation of an action
potential in an adjacent region of the axon membrane.
32. Compare and contrast continuous and saltatory conduction.
33. Outline the factors that alter the rate of action potential propagation along an axon.
SIGNAL TRANSMISSION AT SYNAPSES
34. Describe the structure of a chemical synapse.
35. Go through the sequence of events that allow an action potential on an axon to be
transmitted into a graded potential on a postsynaptic membrane.
36. Indicate the voltage changes associated with EPSPs and IPSPs, and how these potentials
are related to various ion channels.
37. Distinguish between spatial and temporal summation.
38. Note that there must be a mechanism to diminish neurotransmitter concentrations in the
synaptic cleft to be able to turn the stimulus off.
NEUROTRANSMITTERS
39. Describe and give examples and functions of the various neurotransmitter classes.
40. Be able to identify the group to which a specific neurotransmitter belongs.
41. Describe the effect of various drugs and disorders on normal neurotransmitter function.
CIRCUITS IN THE NERVOUS SYSTEM
42. Describe the various types of neuronal circuits in the nervous system.
Chapter Lecture Notes
Homeostasis
The Nervous System is the body's most rapid means of maintaining homeostasis (maintenance of
constant internal environment)
Structural Classification of Nervous System
Central nervous system (CNS) (Fig 12.1)
Brain - 100 billion neurons (each synapse with 1,000 -10,000 other neurons)
Spinal Cord
Peripheral nervous system (PNS) - communication between CNS and rest of body (Fig 12.10)
Structural Divisions
Cranial nerves (12 pairs)
Spinal nerves (31 pairs)
Functional Divisions (uses both cranial and spinal nerves)
Somatic nervous system
Controls skeletal muscle
Voluntary
Autonomic nervous system
Sympathetic division (responds to short term stress)
Parasympathetic division (returns body to normal functions following stress)
Controls smooth muscle, cardiac muscle and glands
Involuntary
Enteric Nervous System
Controls smooth muscle and glands of the digestive system
Involuntary
Functional Classification of Nervous System
Sensory (Afferent) = Input - senses changes in external and internal environment & transmits
changes via sensory neurons/afferent neurons to CNS
Integrative (Processing) - Interprets changes (solely in CNS)
Motor (Efferent) = Output - Responds to changes in form of muscular contraction/gland
secretion via motor neurons/efferent neurons
Neurons
Neurons – specialize in conducting action potential (nerve impulse)
Amitotic but high rate of metabolism that requires abundant supply of O2 and glucose
Parts of a Neuron (Fig 12.2 & Table 12.3)
Cell body
Clustered into ganglia in PNS
Clustered into nuclei in brain
Clustered into horns in spinal cord
Contains nucleus
Contains Nissl bodies - rough ER - site of protein synthesis
Contains neurofibrils - cytoskeleton that extends into axons and dendrites and used to
transport neurotransmitters, nutrients, etc
NOTE: herpes, rabies, and polio viruses and toxin from Clostridium tetani travels
along neurofibrils of axons to cell bodies where they can multiply and cause
damage
Dendrites
Extensions that receive information along with the cell body in motor neurons and
interneurons or generate input in sensory neurons (once extension becomes
myelinated, it is then called an axon) (Fig 12.4)
Axons
Conduct action potentials toward the axon terminal
Distal end of axons swell into synaptic end bulbs that contain neurotransmitters in
synaptic vesicles
Bundles of neuron axons in CNS = tracts (axons bundled with neuroglia)
Bundles of neuron axons in PNS = nerves (axons bundled with
endoneurium/perineurium/epineurium)
Frequently myelinated in both CNS and PNS
Structural Classification of Neurons
Structural classification: classification of neurons according to the number of process from the
cell body (Fig 12.3, 12.4 & 12.5)
Unipolar neuron - one process from cell body
Sensory or afferent in function
Begins as a bipolar neuron in embryo but fuses into single extension
Bipolar neuron - 2 extensions from cell body
Examples: rods and cones (shapes of dendrites) of retina, olfactory neurons, inner ear
neurons
Multipolar neuron - many extensions from cell body
Most of CNS (interneurons) and all motor neurons
Functional Classification of Neurons
Functional classification: classification according to the direction which impulses are conducted
relative to the CNS (Fig 12.10)
Sensory (afferent) neuron - strictly PNS - transmit impulses toward CNS from receptors
Includes both unipolar and bipolar neurons
In unipolar neurons, cell bodies are just outside the spinal cord in a structure called the
posterior (dorsal) root ganglia
Motor (efferent) neuron - transmits impulses away from CNS to muscles/glands
Cell bodies are in spinal cord
All are multipolar
Interneurons (association) neuron - all are found totally within the CNS
All are multipolar
Make up 90% of total neurons
Neuroglia = Glial cells
Neuroglia - support, connect, and protect the impulse conducting cells of the nervous system
(neurons) in both CNS and PNS
Cancer of NS - (gliomas) involves neuroglia and not neurons because neuroglia have retained
mitotic ability but neurons have not retained mitotic ability beyond infancy
Neuroglia outnumber neurons by 5 - 50 X
Neuroglia from CNS (Fig 12.6)
Astrocytes – star shaped
Twine around neurons to form supporting network
Attach neurons to blood vessels
Create blood-brain barrier
Produce "scar tissue" if there is damage to CNS
Microglia - derived from monocytes
Become phagocytic and remove injured brain or cord tissue
Ependymal cells - epithelial cells that line ventricles of brain and central canal of cord
Ciliated to assist in circulation of CSF
Oligodendrocytes - similar to astrocytes but have fewer extensions
Produce myelin sheath in CNS
Neuroglia from PNS (Fig 12.7)
Schwann cells - produce myelin sheath in PNS
Satellite cells - support cell bodies in PNS
Myelin Sheath
Myelin sheath produced around an axon by the following two neuroglia cells
Oligodendrocytes
CNS
Can myelinate up to 15 different neurons (axons)
Schwann cells
PNS
Can have up to 500 Schwann cells along the longest neurons (myelinate only one axon)
Myelin sheath = multilayered lipid and protein covering surrounding axons in PNS and CNS
(actually multilayers of cell membrane from Schwann cell or extension from
oligodendrocyte)
Myelin sheath electrically insulates the axon and increases speed of nerve impulse
conduction (action potential)
Schwann cell wraps like a jelly roll so that up to 100 layers of the cell rolls around the axon
The outer part of the cell contains the nucleus and the Schwann cell membrane (Fig 12.8)
The Schwann cell membrane is called the neurolemma
Evidence has shown that the neurolemma aids in repair and regeneration of axons in the
PNS (absent in CNS) (Fig 12.29)
Guillain-Barre Syndrome – demyelination of axons in the PNS by macrophages
macrophages destroy Schwann cells which can regenerate
person suffers from acute paralysis but most patients recover completely
Oligodendrocytes have "octopus-like extensions" that wrap several different axons and
therefore do not have neurolemma (may be one reason why CNS neurons don't
regenerate) (Fig 12.6)
Multiple Sclerosis - autoimmune disorder in which Killer T-cells destroy
oligodendrocytes that are replaced by plaques (scleroses) from astrocytes
Interferes with impulse transmission
MS is also known as a demyelination disorder of the CNS
Nodes of Ranvier - gaps in myelinated neuron where myelin absent (Fig 12.2 & 12.7)
Nodes of Ranvier are produced by both Schwann cells as well as oligodendrocytes, so nodes
of Ranvier are present in both CNS & PNS
White matter - cell processes (axons) with myelin (Fig 12.9)
Nerve fiber - general term for myelinated axon in both CNS and PNS
Gray matter - parts of neuron, especially cell bodies and dendrites, that lack myelin
Always located in protected areas of CNS
Ganglia would also be gray because cell bodies are not myelinated
Neurophysiology
Action potential - An electrical signal that propagates along the membrane of a neuron or muscle
fiber
Neurophysiology = Excitability - ability to respond to a stimulus (stimulus – any condition
capable of altering the cell’s membrane potential) and convert it into an action potential
Nerve conduction of action potentials involves an electrochemical mechanism
Ion Channels
Proteins in the cell membrane
Don’t require ATP - movement of ions is by channel-mediated facilitative diffusion (Fig 12.11 &
Table 12.1)
Nongated
Leakage channels - randomly open
Cell membranes of muscle/neurons have more K+ leakage channels than Na+ leakage
channels
Gated - channels open and close in response to some stimulus
Chemical (ligand) gated - open and close in response to chemicals like neurotransmitters,
hormones, ions (dendrites and cell bodies)
Mechanically gated - open and close in response to mechanical vibration or pressure such
as sound waves or pressure of touch/stretch (dendrites of sensory neurons)
Voltage gated - open and close in response to voltage (axons only)
Require ATP - movement of ions is by active transport
Na+K+ Pump (Na+K+ ATPase) - movement of three Na+ ions out of the cell and two K+ ions
into the cell by active transport which requires ATP
Resting Membrane Potential (RMP)
Nonconducting neuron has a RMP of -70mV (Fig 12.12)
Reason for resting membrane potential (Fig 12.13)
The inside of the membrane has non-diffusible anions (-) (phosphate and protein anions)
K+ ions are more numerous on the inside than outside – Remember
Na+ and Cl- ions more numerous outside
Small amounts of K+ move to the outside through leakage (nongated) channels with anions
following (cannot diffuse through the membrane and get stuck at the membrane)
Note: there are more K+ leakage channels than Na+ leakage channels
The inside of the cell has a more negative charge than the outside which is positive; overall
the inside of the membrane is -70mV
Maintain resting membrane potential with Na+K+ Pump
Membrane is said to be polarized because of the difference in charge across the membrane =
resting membrane potential
K+ is inside, Na+ is outside, Inside = (-)
All or None Principal
All or None Principle - Neuron transmits action potentials according to all or none principle
If the stimulus is strong enough to generate an action potential, the impulse is conducted
down the neuron at a constant and maximum strength for the existing conditions
Stimulus must raise membrane potential to less negative than -55mV (Threshold potential)
(Fig 12.19)
Graded Potentials
Graded potentials – local potentials (Table 12.2)
Affected at site of stimulation and effect decreases with distance
Spreads passively
The stronger the stimulus, the greater the change in potential and the larger area affected (Fig
12.16)
The potential change could be either negative or positive (Fig 12.14 & 12.15)
Excitatory stimulus - Increases Na+ into cell making membrane hypopolarized
Partially depolarizes and makes membrane less negative
Causes depolarization (but not to -55 mV)
Single excitatory stimulus usually does not initiate nerve impulse but membrane is
closer to the threshold and more likely to reach threshold with next excitatory
stimulus
Inhibitory stimulus - Increases K+ outward or increases Cl- inward
Makes membrane more negative
Makes the membrane hyperpolarized (as low as -90mV)
Generation of action potential is now more difficult
Must add up all the excitatory and inhibitory stimuli (summation) that are influencing the
neuron to determine if an action potential will be sent (Fig 12.17 & 12.26)
Action Potentials
Action Potential (AP) = rapid change in membrane potential (polarity) that can spread down the
length of the axon
The membrane will depolarize and then repolarize
Only muscle and neurons can produce an AP
In neurons, an AP lasts about 1 ms or less
Propagation of APs down axons = nerve impulses
Steps in generating an Action Potential (Fig 12.18 - 12.20)
1. Depolarization
When a stimulus is applied, if the sum of stimuli is excitatory (mechanical gated or
chemical gated ion channels open and cause a net flow of Na+ into the cell) and
depolarization occurs to threshold potential (threshold = -55mV)
At -55 mV, voltage gated Na+ channels open and Na+ rushes in (Na+ inflow), making the
inside of the cell positive
This is the depolarization (Na+ inflow) phase = normal polarized state is reversed
Inside = (+)
K+ is inside, Na+ is inside, Inside = (+)
2. Repolarization - membrane potential returns to a negative value
Repolarization is due to K+ ions flowing outward (K+ outflow) through voltage gated K+
channels
Voltage gated Na+ channels inactivate and close
Voltage-gated K+ channels open in response to positive membrane and remain open until
membrane potential returns to a negative value
Ion distribution is reverse of that at resting
Inside = (-)
K+ is outside, Na+ is inside, Inside = (-)
Refractory Period - period of time during which an excitable cell cannot generate another
action potential
Voltage gated Na+ channels cannot reopen until they become reactivated
Because ion distribution has not returned to resting, sufficient potential has not built
up on either side of the membrane to generate a new action potential
The refractory period begins at depolarization and continues until the resting
membrane ion distribution is restored
The refractory period can be short (0.4 ms in skeletal muscle) because only a few Na+
rush in and only a few K+ move out with each nerve impulse
3. Restoration of Resting Membrane Potential
Leakage channels allow ions to flow into and out of the cell
The Na+K+ pump also operates in restoring the resting ion distribution by pumping Na+
out of the cell and K+ into the cell
K+ is inside, Na+ is outside, Inside = (-)
4. Propagation of Action Potentials (Fig 12.21)
Each action potential acts as a stimulus for development of another action potential in an
adjacent segment of membrane
The Na+ inflow during the depolarization phase of an action potential diffuses to an
adjacent membrane segment
Increase in Na+ concentration raises the membrane potential of that membrane segment to
the threshold potential, generating a new action potential
Action potentials do not travel but are regenerated in sequence along an axon like tipping
dominos
Refractory period prevents action potential from going backwards
Action potentials continue to be regenerated in sequence until the potential reaches the
end of the axon
Saltatory Conduction
Saltatory conduction - Action potentials are only generated at the Nodes of Ranvier (Fig 12.21)
Action potential will skip from node to node
Ionic movement is inhibited beneath myelin sheath
Conserves energy because Na-K Pump is not needed as extensively because only Nodes of
Ranvier are depolarized and repolarized
Conducts up to 50x faster than unmyelinated neuron
Speed of Impulse Conduction
Speed of impulse conduction (propagation) determined by:
Presence of myelin sheath - the further the nodes are apart, the faster the transmission
Diameter of fiber - the greater the diameter the greater density of voltage gated Na+ channels;
the greater the diameter, the faster the transmission
Temperature - the greater the temperature the faster the transmission
Localized cooling can block impulse conduction; therefore pain can be reduced by
application of ice
Types of nerve fibers based on transmission speed
A fibers - myelinated and large diameter; fastest conduction; in areas where split second
responses can mean survival; speeds up to 280 mph
B fibers - myelinated and smaller diameter; speeds up to 32 mph
C fibers - unmyelinated and smaller diameter; speeds up to 4 mph
Note: B and C fibers are going to and from viscera
Synapse
Synapse - connection between axon terminal and another neuron, muscle (neuromuscular
junction), or gland (neuroglandular junction)
Electrical synapse: ionic current spreads directly from one cell to another through gap junctions
(found in cardiac and smooth muscle)
Chemical synapses: neurotransmitter is secreted from one cell and a second cell responds to it
Flow of information is in one direction
Structure of chemical synapse (Fig 12.22)
Synaptic end bulb of first neuron (presynaptic neuron) = presynaptic membrane
Presynaptic electrical signal is converted to chemical signal
Presynaptic neuron releases neurotransmitter
Synaptic cleft: 20-50 nm gap between neuron and next structure
Impulse cannot jump cleft, therefore, will need chemical transmission in form of
neurotransmitter
Cell membrane of second neuron (postsynaptic neuron) = postsynaptic membrane
Postsynaptic neuron has receptors for neurotransmitter
Postsynaptic neuron receives chemical signal (neurotransmitter) and in turn may generate
an electrical signal (action potential)
Exocytosis of neurotransmitter (Fig 12.23)
When nerve impulse (action potential) arrives at synaptic end bulb, the depolarization phase
opens voltage gated Ca2+ channels
Extracellular Ca2+ flows inward
Increase in Ca2+ inside the neuron, triggers exocytosis of synaptic vesicles
Neurotransmitter enters synaptic cleft
Neurotransmitter can either be excitatory or inhibitory
inhibitory neurotransmitters prevents chaos in nervous system
Neurotransmitters have to be inactivated or transported back into the presynaptic neuron
neurotransmitters must be removed from cleft
Neurotransmitters interact with receptor sites of chemically gated ion channels on the
postsynaptic membrane to produce:
EPSP – excitatory postsynaptic potential - a type of graded potential (Fig 12.24)
Typically results from the opening of chemically gated Na+ channels.
IPSP - inhibitory postsynaptic potential - a type of graded potential
Typically results from the opening of chemically gated K+ channels or Cl- channels.
Summation of EPSP & IPSP = inhibition or excitation
Spatial (multiple synapse stimulation) (Fig 12.25)
Temporal (time)
Integration of EPSP and IPSP is at axon hillock (trigger zone)
Whether a neurotransmitter is excitatory or inhibitory is determined by the postsynaptic
membrane receptor
Must have a mechanism to remove neurotransmitters from synaptic cleft to be able to turn
signal off
Neurotransmitters
At least 75 neurotransmitters (Fig 12.27)
Acetylcholine (ACh) - main neurotransmitter of PNS (not common in CNS)
Excitatory for skeletal muscle
Inhibitory for cardiac muscle
Important in brain for memory consolidation (destroyed in Alzheimer’s)
Adenosine – excitatory in PNS and CNS
Caffeine acts as a competitive inhibitor at adenosine receptors in the brain
Catecholamines
Affect mood
6-C ringed structure with 2 hydroxyl groups and an attached amine
They are degraded by catechol-O-methyltransferase and monoamine oxidase (MAO)
Dopamine (DA)
DA is secreted in specific parts of the brain
Excitatory for emotional response but inhibitory in motor functions
Low levels are associated with Parkinson's
Excess DA associated with schizophrenia
DA seems to be the neurotransmitter involved in addiction to heroin, methamphetamines,
cocaine, marijuana, alcohol, nicotine, caffeine
Cocaine prevents DA reuptake
Norepinephrine (NE)
Found in brain and secreted by sympathetic nervous system
Affects mood
Low levels are associated with depression
Methamphetamines (speed) - prevents NE reuptake
Epinephrine = adrenaline
Secreted by the adrenal gland
Enhances sympathetic nervous system response
Serotonin
Produced from amino acid, tryptophan
High amts in milk and turkey
Serotonin is secreted in parts of the brain and spinal cord
Affects mood
Induces sleep
Aids in memory
Prozac, Paxil, Zoloft, Luvox, Celexa and Lexapro inhibit its reuptake by the presynaptic
membrane
LSD blocks the activity of serotonin
Ecstasy inhibits its reuptake by the presynaptic terminal and induces the presynaptic neuron
to release even more serotonin
Ecstasy also induces the release of norepinephrine and dopamine
Amino acids and Amino acid like compounds
Glycine
Common inhibitory neurotransmitter in spinal cord (1/2 of inhibitory synapses in cord
use glycine)
Tetanus toxin inhibits glycine, causing "lockjaw“
Strychnine blocks glycine receptors, causing the diaphragm to continuously contract
which leads to suffocation
GABA (Gamma aminobutyric acid)
1/2 of inhibitory synapses in spinal cord use GABA
Common inhibitory neurotransmitter in brain (as many as 1/3 of brain synapses use
GABA)
Prevents chaos in nervous system
GABA reduces anxiety
Valium, Xanax, alcohol and barbituates enhance the action of GABA
Treatment for epilepsy is drug that increases GABA
Glutamate (Glutamic acid)
Common excitatory in CNS
Increase in glutamate after stroke may lead to death of neurons because of oxygen
deprivation to glutamate transporters that work by active transport (requires
oxygen for ATP synthesis)
Asparagine (Aspartic acid)
Common excitatory in CNS
Peptides - series of covalently linked amino acids (Table 12.4)
Substance P - neurotransmitter in pain pathways (mediates our perception of pain)
Enkephalins and endorphins - endogenous morphine-like substances
Both are structurally similar to morphine and bind to morphine receptors
Modulate pain by inhibiting release of substance P
Runner’s high
Natural child birth
Certain disorders such as Parkinson's disease, Alzheimer's disease, depression, anxiety,
schizophrenia involves problems relating to neurotransmitters
Circuits
Circuits (Fig 12.28)
Typical neuron receives input from 1,000 to 10,000 synapses
Each presynaptic neuron may branch and synapse with up to 25,000 or more different
postsynaptic neurons
Convergence - single postsynaptic neuron controlled by converging signals coming from 2 or
more presynaptic neurons
Divergence - single presynaptic neuron stimulates many different postsynaptic neurons