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Nervous System: The nervous system allows animals to monitor both the outer and inner world. We’re back to homeostasis. The nervous system has three overlapping functions; 1) Sensory input: conduction of signals from sensory cells to the integration center of the nervous system. Receives the stimulus. Receive the sense. 2) Integration: interpretation of information, carried out by the central nervous system-- the brain and spinal cord. Make sense of the stimulus. Make sense of the sense. 3) Motor output: muscles and other glands. Responds to the stimulus. Respond to the sense. The peripheral nervous system (PNS) connects the central nervous system (CNS) to the rest of the body. The PNS receives and responds and the CNS makes sense of the sense. PNS is divided into two divisions: afferent and efferent. The afferent system will receive information, while the efferent system responds to the stimuli. Nervous system: Cells. There are two main cells of the nervous system: 1) Neurons 2) Supporting cells. Neurons are nerve cells. A group of neurons travel along the same canals and form white fibers called nerves. These cells are the functional unit of the nervous system. They can react to environmental stimuli in specific ways. The nerves that are involved with detection of environmental stimuli are called receptors; some detect major, non-specific stimuli while others detect specific stimuli. Stimulation results in the neuron's being activated. The message is carried to the spinal cord and then on to the brain. Once the message is in the central nervous system the message is decoded, by other neurons. The message is sent back to the spinal chord and down to the motor neurons, where you respond to the stimulus. Neurons come in an array of sizes and shapes. All have a dendrite region. This area receives stimuli from either the environment or another neuron. The dendrites may or may not extend from the cell body (gray matter). The signal moves from the dendrites to the cell body. The cell body contains the nucleus and most of the cell organelles. These organelles produce energy; synthesize organic molecules, specifically the neurotransmitters. Clusters of cell bodies in the brain are called nuclei, and a cluster of cell bodies outside of the brain is called a ganglion. Most of the neurons lack centrioles, so they can’t divide. Although there are neural stem cells as adults, they usually remain inactive. The only active neural stem cells are the olfactory receptors, and the cells in the hippocampus (memory center of the brain). The axon is the trunk of the neuron. It may be very long (in humans, up to 3 feet long), and transmits impulses away from the cell body. The axons of many vertebrate neurons are enclosed by a chain of supporting cells called SCHWANN CELLS (in the peripheral nervous system) or 1 OLIGODENDROCYTES (in the central nervous system) that form an insulating layer called the MYELIN SHEATH. Where the axon meets the cell body is the AXON HILLOCK. The axon may be branched and each branch has an ending called the SYNAPTIC TERMINAL, which relays signals to other dendrites of other neurons thorough chemical messengers called neurotransmitters. The space between the synaptic terminal and the dendrite of the other neuron is called the SYNAPSE. A synapse between a neuron and a muscle cell is a neuromuscular junction. A synapse between a neuron and an endocrine gland is a neuroglandular junction. Movement of material from the cell body to the synaptic terminal called axoplasmic transport. The rabies virus is transported this way through the PNS neurons to the CNS neurons to the brain. Neural impulses are transmitted both chemically and electrically. This can happen because the cell membrane has the ability to pump out certain molecules that have an electrical charge and allow other charged particles in. There is a great diversity of neuron shapes and functions. There are three types of neurons: 1) Sensory neurons communicate information about the external and internal environment. The stimulus is taken to the CNS. 2) Interneurons, which integrate sensory input and motor output. These make synaptic connections only with other neurons. 3) Motor neurons convey impulses from the CNS to effector cells. Neurons are arranged in circuits made up of two or three types of neurons. The simplest circuit involves the synapses between the sensory and motor neurons. The sensory neuron sends a message to the motor neuron and you react. This is called the reflex, a simple automatic response. A cluster of nerve cell bodies (often of similar functions) in the PNS is a ganglion (ganglia— plural). Similar clusters in the brain are called nuclei. Ganglia and nuclei enable the nervous system to coordinate activities without involving the whole CNS. The reflex allows your body to respond to a simple task and allows the brain to focus on more complex tasks. Supporting Cells: Neuroglia Supporting cells outnumber the neurons 10-50 times. These cells are essential for the structural integrity of the nervous system and the normal functioning of neurons. In the CNS, the supporting cells are GLIAL CELLS. There are several types of glial cells. 1) 1) Astrocytes encircle the capillaries in the brain and contribute to the blood-brain barrier. The barrier restricts the passage of most substances into the brain. The extension of Astrocytes end in flattened ‘feet’ that wrap around the capillaries. These feet block substances from entering and leaving the capillary (can control the fluid composition of the brain). These act as a filter to what enters the brain. The Astrocytes can also help repair damaged tissue and help guide neuron development. 2) Oligodendrocytes form insulating myelin sheaths in many cells of the CNS. 3) Ependymal Cells: In the CNS, there is cerebrospinal fluid (CSF) that surrounds and flows through the brain and flows through the central cavity of the spinal cord. Ependymal cells line the 2 areas that come into contact with cerebrospinal fluid. These cells make up the ependyma, some of these cells may monitor the CSF and some cells of the ependyma may be stem cells that can produce more neurons. 4) Microglia: These cells are the smallest and least numerous in the CNS. These cells move around the CNS and clan up the cellular debris, waste products and pathogens. Neuroglia of the PNS: 1) Satellite Cells: These cells have the same functions as the Astrocytes, but these are in the PNS. 2) Schwann Cells: Form the myelin sheaths in the PNS. These cells grow around the axons in a way that they form concentric layers. The lipid sheaths provide electric insulation of the axon. The Resting Neuron: Neural Impulse. The signal transmitted along the length of the neuron is an electrical signal that depends on the flow of ions across the cell membrane. All neurons have a charge difference across the cell membrane. The inside of the cell is more negative than the outside of the cell. Electrodes can measure this difference. This voltage measured across the membrane is the MEMBRANE POTENTIAL and ranges from -50mV to -100 mV. The outside of the cell is called zero, so the negative sign is in reference to the outside of the cell. For a resting neuron, the membrane potential is about -70mV. This is the RESTING POTENTIAL. Because of the selectively permeable membrane, there is a difference in ionic composition between the intracellular and extracellular fluids, called membrane potential. Both the intra and extracellular fluid contains ions. The principle cation (+ charge) outside the cell is Na+ with a small amount of K+. Inside of the cell the main cation is K+ with a small amount of Na+. The main anion (- charge) outside of the cell is chloride (Cl-). There are some Cl- inside the cell; however, inside the cell is a class of negatively charged substances that can be treated as a single group (A-). The ions cannot diffuse across the membrane. They must move through ion channels (by facilitated transport) or be carried by transport proteins (active transport). These channels are selective for particular ions. Cells usually have greater permeability to K+ than to Na+, suggesting that the cell has more potassium channels than sodium channels. Let’s Discuss K+ First: As the K+ finds a concentration gradient, they move through K+ channels. Because the large group of negatively charged molecules (proteins, amino acids, sulfate, and phosphates) cannot leave the cell, the interior of the cell becomes more negative than the outside. The increasing negativity of the inside attracts the K+. If K+ were the only cation moving, then the potential of the inside when the K+ efflux equaled the K+ influx would be -85mV. This is the EQUILIBRIUM POTENTIAL. Let’s Discuss Na+ Now: As Na+ finds the concentration equilibrium, they move through Na+ channels. Some move 3 into the cell making it less negative. This makes the RESTING POTENTIAL -70 Mv. If left unchecked the concentration gradient of Na+ and K+ would disappear, but another type of cell membrane protein called the SODIUM POTASSIUM PUMP. This pump uses ATP to actively transport sodium out of the cell and potassium in the cell. These pumps move 3 Na+ out for each 2 K+ in. As the Na+ is moved out and the K+ is moved in, a concentration gradient is established. Along with this gradient is potential energy. The Na+ wants to move into the neuron and the K+ wants to move out of the neuron. However, the channels have gates. The ions can’t move until the gates open. This potential energy is the membrane potential. There are more K+ channels than Na+ channels. It is easier for K+ to move than Na+. Ion channels: Transmembrane protein channels that are specific for K+ and Na+. These channels control the flow the Na+ or K+. These channels can be active or passive. Passive: Always open. These channels can change their permeability. Depending on the environmental conditions, the proteins can change shape. Active Channels—gated channels: These open and close in response to different stimuli. There are three types: 1) Chemically regulated channels: Specific chemicals bind to the channel (bind to receptors). The channel proteins change shape and open. More abundant on the dendrites. 2) Voltage-Regulated channels: These open and close in response to changes in the membrane potential. There are voltage regulated Na+, K+ and Ca2+ channels. Na+ channels, the two gates function independently. The activation gate opens when stimulated and lets Na+ into the cell. The inactivation gate closes (slowly) and keeps Na+ in the cell (and out of the cell). 3) Mechanically regulated channels: Open and close in response to physical distortion of the membrane surface. This is important for sensory neurons. Action Potential: Neurons have proteins in their membrane called GATED ION CHANNELS. These proteins let the cell change its membrane potential in response to stimuli that the neuron receives. If the stimulus opens up a potassium channel, the membrane potential will be more negative as K+ exits, this is HYPERPOLARIZATION. If the sodium channels open and allow an influx of sodium, the membrane potential will be less negative, this is DEPOLARIZATION. The voltage changes caused by this are called GRADED POTENTIALS. A large stimulus will open more channels and produce a larger change in permeability. This is called a local current; a small area on the neuron is affected by the stimulus. When the neuron receives a stimulus, the Na+/K+ pump stops. In order for a neuron to depolarize, a threshold must be met. If a cell is depolarized to the threshold an ACTION POTENTIAL results. The threshold potential is 15-20 mV more positive than the resting potential and varies for different neurons. We’ll say that the threshold value will be –55 mV. 4 The action potential (another term for depolarization) is an ALL OR NONE EVENT. Once the threshold is met, an action potential is triggered. When that happens, all the Na+ gated channels in an area open. Na+ rushes in due to the potential energy of the neuron. The membrane actually reverses polarity, and increases to +30mV. The neuron must reestablish the resting potential. Repolarization follows. The K+ channels open and K+ rushes out due to the potential energy. Too much K+ will leave the neuron and the charge drops below –70mV. This is called the UNDERSHOOT and is corrected quickly. The Na+/K+ pump reestablishes the Na+ and K+ gradient. The whole event is over in a millisecond. The action potential comes about because of voltage-gated channels which open and close in response to membrane potential. The two types of these channels contribute to the action potential are the SODIUM AND POTASSIUM CHANNELS. Each K+ channel has a single voltage-sensitive gate. It is closed at resting and opens slowly when depolarization occurs. The voltage-gated sodium channels have two gates that are voltage sensitive. The activation gate responds to depolarization by quickly opening. The inactivation gate responds to depolarization by slowly closing. At resting, the inactivation gate is open and the activation gate is closed. When the cell is depolarized, the activation gate quickly opens and the sodium rushes into the cell, thereby depolarizing the cell. More sodium gates open causing more depolarization (positive feedback). The opening and depolarizing happens until all the sodium channels are open. When the cell repolarizes, the sodium-channel inactivation gate has closed, thus no more Na+ can enter the neuron. The voltage sensitive potassium channels open in response to depolarization, which allows the K+ to flow quickly out of the cell. This helps restore and internal negativity of the resting neuron. If a second stimulus tries to stimulate the cell during repolarization, the cell will not respond. This is called the REFRACTORY PERIOD. The slow closing of the K+ channels contributes to the undershoot by not being able to close quickly enough—too much K+ leaves the neuron. How do neurons distinguish strong stimuli from weaker ones? Strong stimuli result in a greater frequency of action potentials. Movement of the Action Potential: A neuron is stimulated at its dendrites of the cell body, and the action potential travels along the axon to the end of the cell. An action potential in one area causes the next area of the neuron to depolarize above the threshold, which triggers a new action potential at that position. This will cause the next area to be depolarized and so on. Speed of the Action Potential: One feature that affects the speed of the action potential is the diameter of the axon. The larger the diameter the faster the speed of transmission. 5 Another way to increase the action potential speed is by use of myelinated axons. The myelin sheaths have small gaps called the NODES OF RANVIER between neighboring Schwann cells. The voltage sensitive ion channels are concentrated in these node regions. The flow of ions can only occur at these regions. The action potential jumps from node to node, thus skipping the insulated regions. This is SALTATORY CONDUCTION, which is a faster transmission of the impulse. Axons are classified into three groups due to the diameter, methylation, and speed. 1) Type A fibers: These fibers have the largest diameter (between 4–20 m) and are myelinated. The impulses moving through these fibers at a speed of 140 m/sec or 300miles/hour. These fibers usually carry info to CNS about position, balance, delicate touch, and pressure… 2) Type B fibers: These fibers are smaller myelinated axons of 2-4m. The speeds of these action potentials reach 18 m/sec or 40 miles/hour. 3) Type C fibers: These are small (less than 2m in diameter) unmyelinated neurons that have a speed of action potential of 1m/sec or 2 miles/hour. Both type B and type F fibers carry information to the CNS that respond to temperature, pain, general touch, and these fibers carry information to smooth muscles. Not every neuron can be type A, you would be too large. In fact, only 1/3 of our neurons are type A. Most sensory information is carried by Type C neurons. Your body has prioritized; urgent information for survival is conducted by type A fibers. Less urgent information is moved by type B or C fibers. Review: If there is sufficient stimulus (above the threshold), then the neuron changes. 1) At any dendrite that receives a stimulus, the sodium pump stops briefly, less than a millisecond. 2) The Na+ rushes into the negatively charged interior, and the threshold is met (-55 mV). 3) All the Na+ channels of an area open the Na+ rushes in. The polarity of the inside of the cell changes from -55 mV to +30 mV (which is a total of +100 mV change). The cell is depolarized. This process of depolarization is called the action potential. 4) Depolarization of one area causes the Na+ channels to open in the next area. The depolarization moves from node to node in a wave like action. 5) Following depolarization, the K+ channels open and the K+ leaves the neuron. Too much K+ leaves the cell, the undershoot, which is quickly corrected. 6) The Na+/K+ pump reestablishes the concentration gradient. Synapse and the Synaptic Junction: The synapse is the space between cells of the nervous system. The transmitting cell is called the presynaptic cell and the cell receiving the stimulus is the postsynaptic cell. There are two types of synapses: electrical and chemical. 1) Electrical Synapses allow the action potentials to spread directly from the presynaptic to 6 postsynaptic cell. Gap junctions connect these cells. These channels allow the local ion currents of an action potential to flow between the neurons. The cells allow the impulse to travel from neuron to neuron without delay and no loss of signal strength. These are not as common as the chemical synapse. 2) Chemical Synapses have a narrow cleft or gap that separates the presynaptic and postsynaptic cells. A series of events at the synapse converts the electrical signal of an action potential to a chemical signal and back to an electrical signal in the postsynaptic cell. On the presynaptic cell there is a swelling at the end of a branch called the SYNAPTIC TERMINAL. Within the synaptic terminal are numerous sacs called SYNAPTIC VESICLES that contain thousands of NEUROTRANSMITTER MOLECULES. When an action potential arrives at the synaptic terminal and depolarizes the presynaptic membrane, the vesicles move to the membrane that faces the cleft. Once depolarized Ca2+ moves into the cell through voltage channels. The sudden increase of calcium ions stimulates the synaptic vesicles to fuse with the presynaptic membrane and spill the neurotransmitter into the cleft by exocytosis. The neurotransmitter travels a short way to the postsynaptic membrane. The specific receptors that extend from the cell membrane on the postsynaptic membrane receive the neurotransmitters. These receptors are connected with selective ion channels that open and close controlling which ions exit and enter the cell. When a receptor binds to a neurotransmitter, it opens the ion channel that allows K+, Na+ and Cl- to cross the membrane. The effect of the neurotransmitter on the postsynaptic membrane depends on the properties of the receptors, not the neurotransmitter. Enzymes quickly break down the neurotransmitter into smaller components that are recycled by the presynaptic cells. The neurotransmitters are pumped back into the presynaptic cells. The chemical synapses allow for signals to travel one way. The synaptic cells can also integrate information made of excitatory and inhibitory signals. Cholingergic Synapse: These are synapses that release Acetylcholine (Ach). The most common and best-studied neurotransmitter. This neurotransmitter is released at all neuromuscular junctions, at many synapses in the CNS, at neuron-to-neuron synapses in the PNS, and at neuroglandular junctions. When Ach is released into the synapse, the amount of Ach controls the number of Na+ channels opened in the postsynaptic cell. Ach is removed by acetylcholinesterase. In fact, about ½ of the Ach is broken down before it reaches the receptors. Once bound to the receptors, Ach is broken down right away (within 20 milliseconds) to acetate and choline. The choline is absorbed by the presynaptic bulb and used to make more Ach. Acetate is absorbed by the postsynaptic cell and is used by the cell. How the Neurons Integrate at a Cellular Level: A neuron may receive information from many different neurons. Some messages will be inhibitory 7 and others will be excitatory. How a neuron reacts depends on the ability to integrate the positive and negative signals. At an excitatory synapse, the neurotransmitter receptors control gated channels that allow Na+ to enter and K+ to leave. There is a net flow of positive charges into the cell, which depolarizes the cell. This is an EXCITATORY POSTSYNAPTICAL POTENTIAL (EPSP). At an inhibitory synapse, the neurotransmitter molecules causes the cell to become hyperpolarized by making the membrane more permeable to K+, which rushes out or Cl- which moves in. This makes it more difficult for the threshold to be reached. This is called the INHIBITORY POSTSYNAPTIC POTENTIAL (IPSP). A single EPSP at one synapse is usually not strong enough to trigger an action potential. Usually, several synapses acting at the same time on the same postsynaptic cell can induce a cell to depolarize. The additive effect of postsynaptic potentials is called SUMMATION. There are two types of summation: 1) Temporal summation occurs when chemical transmissions from one or more synaptic terminals occur so close together in time that each potential particularly depolarizes the membrane before the voltage returns to the resting potential after the prior stimulation. 2) Spatial Summation occurs when several different synaptic terminals, usually belonging to different presynaptic neurons, stimulate the postsynaptic cell at the same time. The axon hillock is the neuron’s integration center. This area takes an average of all the IPSPs and EPSPs and responds accordingly. When there are more EPSPs than IPSPs, the threshold is met and the neuron depolarizes. If the IPSPs are greater than the EPSPs, then the neuron is inhibited. Neurotransmitters and Receptors: For a compound to be recognized as a neurotransmitter, it must meet three criteria. 1) The presynaptic cell must contain the specific compound, which will affect the membrane potential of the postsynaptic cell, in synaptic vesicles and when properly stimulated, discharge the substance. 2) The compound should be an EPSP or IPSP when artificially injected into the synapse. 3) The substance must be removed quickly from the synapse by either enzymes or the cell. Types of Neurotransmitters: 1) Acetylcholine (ACh) is a common neurotransmitter. ACh is released at the neuromuscular junctions, exciting the motor cells. Another type of Ach can reduce the strength and rate of the cardiac muscles. At other times, ACh can be inhibitory. The effect depends on the receptors found on the postsynaptic membranes. 2) Biogenic amines are neurotransmitters derived from amino acids. Catecholamines are produced from the amino acid tyrosine and include epinephrine (in the CNS), norepinephrine (in the autonomic nerves), dopamine (in the brain), and serotonin 8 (synthesized from the amino acid tryptophan). Most work in the CNS (except for norepinephrine which works in the PNS). Dopamine: if the neurons that produce dopamine are destroyed, Parkinson’s disease is the result. Cocaine inhibits the removal of dopamine from the synapse. Serotonin: a decrease in serotonin can cause depression. Prozac, Paxil, and Zoloft inhibit the reabsorption of serotonin by neurons. Selective Serotonin Reuptake Inhibitors (SSRI) inhibits serotonin reabsorption. This leads to a higher serotonin concentration over time. This makes people happier. LSD binds to the serotonin and dopamine receptors in the brain. FYI: D4DR is a gene on chromosome 11 that produces dopamine receptors on neurons. If there is a decrease in dopamine, you might have Parkinson’s disease—indecisive, frozen personality, can’t initiate your body’s movements. If there is increased dopamine, you are high exploratory and adventurous. D4DR has a minisatellite sequence of 48 bases. If you increase the number of satellites the less response the receptors are to dopamine. People with long D4DR will increase their activities to get a dopamine buzz. If you increase serotonin you will be come compulsive and neurotic (obsessive/compulsive disorder). Prozac affects the serotonin in the body. Chromosome 17 contains the serotonin transporter gene. Interestingly, if you decrease your cholesterol, you will decrease serotonin and increase violent tendencies. 3) Neuropeptides are short chains of amino acids that can serve as neurotransmitters. Endorphins are neuropeptides, which decreases perception of pain. Neuromodulators are usually neuropeptides. These are small protein chains produced by the presynaptic cells that bind to the receptors of the postsynaptic cell, which can activate cytoplasmic enzymes. Examples of neuromodulators are opiods. Opiods are similar to opium and morphine. There are four classes of opiods that have been identified in the CNS: Endorphins, Enkephalins, Endomorphins, and Dynorphins. These opiods relieve pain by inhibiting the release of the neurotransmitter at the neurons that relay pain. 4) Amino acids: there are four known amino acid neurotransmitters in the CNS. GABA: Gama aminobutyric acid (usually has an inhibitory function. About 20% of synapses in the brain release GABA. GABA release decreases anxiety), Glycine, Glutamine, and Aspartate. Most are IPSPs. Some neurons are able to use gas molecules as neurotransmitters. Nitric oxide and carbon monoxide can be used as local regulators. These gases are not stored in vesicles; instead they are produced when needed. Neurotransmitters and neuromodulators have direct and indirect effects on postsynaptic cells when they bind. They have an ionotropic effect, a direct effect, where they open up ion channels. The indirect effect is metatrophic effect, which is a change in metabolic activity. This is done in the same way in the endocrine system. The neurotransmitter/neuromodulator will bind to the receptor and acts as the primary messenger. This activates a secondary messenger, which activates the G protein and forms GTP, this activates adenyl cyclase, which converts ATP to cAMP. 9 Invertebrate Nervous System: The simplest system can be found in the phylum cnidarians. These organisms have a loosely organized net of nerves with no central control. Echinoderms have nerves that branch form the central nerve ring around the oral disk. This system coordinates the movements of the arms. Bilateral animals have a concentration of organs around the anterior end, a trend called CEPHALIZATION. Enlargement of the anterior ganglia would lead to the first brain. Invertebrates show increasing cephalization from flatworms to annelids to arthropods. Vertebrate Nervous System: It is divided into different parts, the Central Nervous System (CNS), which processes information, and the Peripheral Nervous System (PNS), which carries the information. The Peripheral Nervous System: Consists of two separate groups of cells 1) In the sensory division, are afferent cells, which brings information into the central nervous system. 2) In the motor division, are efferent cells, which carries signals to the muscle cells. The motor nervous system has two divisions with separate functions: 1) The Somatic Nervous System carries signals to skeletal muscle following a response to external stimuli. This system is voluntary but a substantial portion of the skeletal muscle movement is actually determined by reflexes (a reflex is an automatic reaction to a stimulus). 2) The Autonomic Nervous System regulates the internal environment by controlling smooth and cardiac muscles, the organs of the gastrointestinal tract, the cardiovascular system, the excretory system, and the endocrine system. The control is usually involuntary. There are two divisions of the autonomic nervous system: a) The sympathetic, which increases the energy expenditure and prepares an individual for action. b) The parasympathetic, which gains and conserves energy. When the two go to the same organ, they are antagonistic to each other. Central Nervous System: CNS It forms the bridge between the sensory and motor functions of the peripheral nervous system. There are two main divisions: 1) Spinal cord, which is inside vertebral column 2) Brain which is on top of the spinal cord and is the center for integration of homeostasis, perception, movement, intellect, and emotions. The CNS is covered by MENINGES. These are three layers of protective connective tissue (pia 10 mater, dura mater and arachnoid mater). The dura mater is the outermost covering of the spinal cord and brain. This layer is made up of dense collagen fibers. The dura mater is in contact with the arachnoid mater. The inner layer of the dura mater and the outer layer of the arachnoid mater is covered with squamous epithelial cells. The middle layer is a network of collagen and elastin fibers. The pia mater is the inner layer and this is made up of collagen and elastin fibers that are bound to the nerves underneath. The blood vessels that service the CNS run along this layer. Neurons in the CNS are located in bundles. The myelin sheath gives them a white appearance, which is called white matter/inner region. The outer region is the gray matter which are the pathways going to the cell body. The cell bodies are organized into functional groups called nuclei. Sensory nuclei receive information and motor nuclei control the peripheral nerves to respond. The spinal cord is so organized that we can predict which muscles will be affected by damage done to a specific area of gray matter. Surrounding each spinal nerve is a series of connective tissue, which is comparable to a skeletal muscle. The outer layer is the epineurium, which is a dense network. The perineurium is the middle layer of connective tissue that divides the nerves into a series of compartments that contain axon bundles. The endoneurium is the inner layer that extends from the perineurium and surround individual axons. The blood vessels that feed the neurons are found here. There are ventricles, which are fluid filled spaces in the brain that connect with the narrow central canal of the spinal cord. The spaces are filled with cerebrospinal fluid, which the brain forms by filtering the blood. The cerebrospinal fluid absorbs shock, cushions the brain, and carries nutrients, hormones, and white blood cells to different parts of the brain. The cerebrospinal fluid flows through the ventricles and central canal and empties back into the veins. The Spinal Cord has two main functions: 1) Integrates simple responses to certain stimuli. 2) Carries information to and from the brain. Neuronal Pools: The billions of interneurons of the CNS are organized into smaller neuronal pools. These are functional groups of interconnected neurons. A neuronal pool may involve neurons in several regions of the brain, or may be restricted to one specific location. There be hundreds to thousands of neuronal pools. Each pool has a limited number of input sources and output destinations. They may contain both inhibitory and excitatory neurons. The pattern of interactions between neurons is important to the function of the neuronal pool. There are five patterns of neural interactions. 1) Divergence: when one neuron stimulates several neurons, or one pool stimulates many pools. For example, when visual information is brought into brain, which spread out the information. 2) Convergence: Several neurons stimulate one neuron. Through convergence, the same motor neuron can be stimulated. 3) Serial processing: The impulse in a step-wise fashion, from one neuron to the next. This occurs when the sensory information is relayed from one part of the brain to the next. 4) Parallel processing: Several neurons or neuronal pools process the same information at the 11 same time. Divergence takes place and many responses can occur at the same time. As someone throws a ball at your head, you are able to raise your arm, duck your head, close your eyes, and yell at the person who threw the ball—all at the same time. 5) Reverberation: A branch of an axon will extend back to the source of the impulse and stimulate the neuron. This is a positive feedback loop. Once activated the circuit will continue to fire until fatigued or an inhibitory stimulation breaks the cycle. The spinal integration is usually a reflex, as sensory nerve carries information up to the spinal cord where it connects with a motor neuron. Reflexes are rapid autonomic responses to a specific stimulus. Reflexes maintain homeostasis by making rapid adjustments in the function of organs or organ systems. The response has little variability. The reflex arc starts with the receptor cells receiving a stimulus. The sensory neuron will depolarize with the stimuli. The information gets to the spinal cord and integration occurs here. An impulse is sent back to the motor neuron and you respond with a muscle contraction or stimulation of an endocrine gland. This is an example of negative feedback. You are born with innate reflexes and some reflexes can be acquired, learned reflexes. The Brain: Brain is an over development of one end of the nervous system. Development of the Brain: Advanced planarians have a longitudinal, bilaterally symmetrical body plan composed of two nerve cords. A concentration of neurons, called a ganglion, in the head region. The ganglion can be seen as a precursor to a brain. Annelids have a large ganglion, which is surrounded by the esophagus in the head of the worm. Each segment has a pair of fused ganglia. Mollusks: The octopus has a ganglionic mass of neural tissue around the esophagus. Arthropods have a brain that is composed of ganglia above and below the esophagus. Each brain part has a specific role. Echinoderms have a nerve ring around the mouth. Five nerve tracks in some groups the nerve trunks consist of specialized neuroectoderm. However, there are no ganglionic masses of nerve tissue. Brains of Vertebrates: There are three parts of any vertebrate brain: The forebrain is the cerebrum. The midbrain senses the visual and olfactory stimuli. The hindbrain controls the involuntary actions. Chondrichthyes: Sharks have a small cerebrum. If it is removed, the shark shows little or no change in behavior. A large part of the brain is devoted to smell. 12 Osteichthyes: bony fish brains are more differentiated. If the cerebrum is removed, it causes alterations in their behavior. The Human Brain: The adult brain contains about 985 of the body’s neural tissue. The volume of an average brain is about 1600 ml (range of 750 – 2100 ml). The male brain is about 10% larger than the female brain, due to the difference in body size. Major brain structures: The forebrain contains the two cerebral hemispheres and the internal structures which include the thalamus and hypothalamus. The mid brain is between the forebrain and hindbrain. The hindbrain is made up of the medulla, cerebellum and pons. 1) The adult brain is dominated by the cerebrum, divided into two hemispheres, and covered by the neural cortex (superficial layer of gray matter). Each hemisphere contains ridges (gyri or gyrus), shallow depressions (sucli or suclus), and deeper grooves (fissures). The cerebrum is the seat of higher mental functions: thoughts, sensations, intellect, and complex movement. 2) Cerebellum: the second largest structure of the brain. It has hemispheres, but you can’t see them, because a layer of gray matter called the cerebellar cortex covers the cerebellum. This structure adjusts movements by comparing arriving information with previously experienced movements, and allows you to perform the same movements over and over again. 3) The last major anatomical region can be examined after the cerebrum and the cerebellum have been removed. The diencephalon is composed of the right and left thalamus, the relay and processing centers of the sensory information. The hypothalamus is the floor of the diencephalon, and monitors the body and controls almost every system. A narrow stalk connects the hypothalamus to the pituitary gland. 4) Brain Stem: This structure includes the mesencephalon, pons, and medulla oblongata. The mesencephalon is called the midbrain and processes visual and auditory information and controls the reflexes triggered by those two senses. This region also helps you maintain your consciousness. The Pons connects the cerebellum to the brain stem. The pons help the medulla regulate the breathing, and contains nuclei involved with the somatic and visual motor control. Medulla Oblongata is where the spinal cord connects with the brain. The medulla relays information to the thalamus and regulates autonomic functions: heart rate, blood pressure, digestion, swallowing, breathing (with pons), and vomiting. Protection and Support: Cranial Meninges: The dura mater is the outer layer and is attached to the periosteum of the cranial bones, the skull. There is a gap between the dura mater and the arachnoid mater, which is filled with cerebrospinal fluid (CSF) and blood vessels. The pia mater is connected with the arachnoid mater and the brain. The pia mater is anchored to the brain with Astrocytes. 13 There is about 500 ml of CSF produced per day, with a total of about 150 ml of CSF at anyone time in the CNS. The meninges hold the brain in place, and the CSF cushions the brain, as well as, carries nutrients, hormones, and white blood cells to different parts of the brain. Blood-Brain Barrier (BBB): The CNS is isolated from the circulatory system by the BBB. The BBB occurs for two reasons: 1) tight junctions that occurs between the endothelial cells of the brain capillaries. 2) Astrocyte ‘feet’ encircle the capillaries and block what enters and exits the capillaries (also produce chemicals). Substances must pass through two layers of cells to get in and out of the brain. In general, only lipid soluble compounds: CO2, O2, NH3, lipids, steroids, prostaglandins, and small alcohols can diffuse across the membrane. Other compounds need to move through by active or facilitated transport. The choroid plexus (center of the brain that produces CSF) has no astrocytes since it’s not neural tissue. The choroid plexus is lined with ependymal cells with tight junctions. These cells produce CSF and surround the capillaries of the choroid plexus. This is the Blood-CSF barrier. The BBB remains intact through out the brain throughout the brain except for these 4 exceptions. 1) Hypothalamus is exposed to blood. 2) Capillaries that associate with the posterior pituitary. 3) Capillaries that associate with the pineal gland. 4) Capillaries at the choroid plexus, however they have the Blood-CSF barrier. Brain Stem: The brain stem controls data conduction and autonomic activities essential for life. There are three parts that make up the brainstem: Medulla Oblongata: controls breathing, heart rate (strength of contractions) and blood vessel activities (controls the flow of blood through the peripheral tissue), swallowing, vomiting, and digestion. The medulla also controls the muscles of the pharynx, neck and back and thoracic and peritoneal organs. The medulla will pass information to the thalamus. Pons: regulates breathing centers in the medulla. The pons is the portion of the brain stem, above the medulla that connects the cerebellum to the cerebral cortex. The cerebellum controls balance, equilibrium, and coordination. The cerebellum also learns and remembers motor responses, and is responsible for hand-eye coordination. The cerebellum will refine learned movement patterns. Midbrain: Mesencephalon contains centers that receives and integrates types of sensory information. The midbrain initiates activities to the visual and auditory stimuli. This also serves to send sensory information to parts of the forebrain. The reticular formation system is found here. This is a system of neurons that regulates sleep and arousal. Part of this system is the reticular activating system (RAS). The RAS acts as a sensory filter and filters out what goes to the cerebral cortex. Diencephalon plays a huge role in integrating the conscious and unconscious sensory information and motor commands. There are three parts to the diencephalon: epithalamus, thalamus, and 14 hypothalamus. Epithalamus is the root of the diencephalon and contains the choroid plexus and the pineal gland (secretes Melatonin and responsible for the body cycles). The thalamus is the final relay point for sensory information. The thalamus filters the senses. It consists of densely packed clusters of neurons and connects different parts of the brain. The thalamus contains the reticular system, which is an area of interconnected neurons, which may activate the appropriate parts of the brain. Then receives impulses from the cerebrum and determines where these impulses go. The thalamus is also responsible for receiving information from the cerebrum that regulates emotion and arousal. The thalamus has three functions: 1) part of the limbic system, involved with emotion and motivation, 2) connects the emotional centers in the hypothalamus to the cerebrum, 3) relays sensory information about touch, pressure, vision, sound, pain, temperature, and body position to the cerebrum. The hypothalamus is small and densely packed with cells. It is important in regulating the internal environment as well as general aspects of behavior. It is located above the optic chiasma. Here are some of the functions of the hypothalamus: 1) regulates somatic motor patters associated with rage, pleasure, pain and sexual arousal by stimulating portions of the brain. For example, the facial expressions associated with rage is controlled by the hypothalamus; 2) controls the activities of the autonomic centers of the pons, and medulla oblongata that regulates the heart rate, blood pressure respiration, and digestion; 3) coordinates the activities of the neural system and endocrine system by producing trophic hormones; 4) produce antidiuretic hormone and oxytocin; 5) specific hypothalamus cells can produce sensations that lead changes to behavior—feeding and thirst centers; 6) coordinate the voluntary and autonomic functions—when you prepare for dangerous situations; 7) regulates body temperature; and 8) coordinates the circadian rhythm. Limbic System: This is the border between the diencephalon and the cerebrum. Functions of the limbic system: 1) Establishes the emotional states. 2) Links the conscious intellectual functions with the unconscious autonomic functions of the brain stem. 3) Memory storage and retrieval. The amygdala and hippocampus are found in the limbic system. The amygdala is responsible for organizing the emotional information and the hippocampus is responsible for memory storage and retrieval. The cerebrum is the largest region of the brain and is the center of intelligence. The more the cerebrum convolutes, the more the surface area of the cerebrum increases. The cerebrum is mostly involved with the processing of sensory and motor information. The two hemispheres are equal in potential, but not identical. A blanket of neural cortex covers the 15 paired hemispheres. The primary route of communication between the right and left cerebral hemispheres is the corpus callosum. If this is cut, the halves cannot communicate. Each hemisphere can be divided into lobes or regions named after the bones of the skull: frontal lobe, parietal lobe, temporal lobe, and occipital lobe. There are three points about the cerebral lobes: 1) Each cerebral hemisphere releases sensory information from and sends motor commands to the opposite sides of the body. 2) The two hemispheres have different functions. 3) The correspondence between a specific function and a specific region of the cerebral cortex is imprecise. Parts of the Cerebrum: Basal Nuclei: This part of the brain is also called the basal ganglia. The basal nuclei is responsible for motor coordination, planning and learning motor sequences. The basal nuclei directs the activities of the diencephalon and brain stem. The subconscious control of skeletal muscles and coordination in learned movement patterns. Information arrives the basal nuclei from the thalamus and then is transferred to the appropriate areas of the cerebral cortex. Motor and Sensory Area: Primary motor cortex is part of the frontal lobe and is responsible for the voluntary control of the skeletal muscles. The primary sensory cortex is found in the parietal lobe. The thalamus relays information to the primary sensory center (pressure, pain, vibration, and temperature). The thalamus also directs sight sound, smell and taste the appropriate centers—visual cortex (occipital lobe), auditory cortex (temporal lobe), olfactory cortex (temporal lobe), and Gustory complex (taste is adjacent to the frontal lobe). The sensory and motor regions are connected to the nearby association areas—region that interprets the data or coordinates a motor response. The information arrives to the sensory cortex and the somatic sensory association area monitors the information that arrives and interprets it. Each sense has its own association area. When you look at the letters on the page, the visual association area interprets the results. Your visual cortex sees the symbols on the paper; the visual association area decodes the symbols and makes sense of the letters (puts them into words). The somatic motor association area, premotor cortex, is responsible for coordination of learned movements. The primary motor cortex does nothing until stimulated by other neurons in the cerebrum. The information is relayed to the primary motor cortex by the premotor cortex. With repetition, you store a pattern of movement in the premotor cortex. Integrative Centers: These are centers that receive information from many association centers and direct complex motor activities. These centers are located in the lobes and cortical areas of both cerebral hemispheres and are concerned with the performance of the complex tasks of speech, writing, and math, understanding spatial relationships. These functions can be restricted to one hemisphere. 16 The General Integrative area: Wernicke’s area. This area receives information from all the sensory association areas. This is usually present in the left hemisphere. This region plays a role in your personality by integrating sensory information and coordinating access complex visual and auditory memories. The Speech Center: Broca’s area. This area is usually in the left hemisphere at the edge of the premotor cortex. This coordinates all the muscles in speech. The Prefrontal Cortex: Coordinates information relayed from the association areas of the entire cortex. This area performs abstract intellectual factors such as predicting the consequences of events or actions. This area has extensive connections with other cortical areas with other portions of the brain. Feelings of frustration, tension, and anxiety are generated in the prefrontal cortex. Hemispheric Lateralization: Each hemisphere is responsible for specific functions that are not usually performed by the other hemisphere. Left Hemisphere: Wernicke’s area, Broca’s area, reading, writing, and speaking are found in the left hemisphere. In right-handed people, the Left premotor cortex is responsible for control of the right hand. This area is larger. Analytical tasks, mathematical calculations and logical decision making occurs in the left hemisphere. Right Hemisphere: Analyzes sensory information, relates body toe the sensory environment, identifies objects by touch, smell, sight, taste and feel. For example, this membrane allows you to recognize faces and understand 3-D relationships. For left-handed people, the right premotor cortex is larger and controls the left hand. The right hemisphere controls spatial visualizations and emotions. FYI: 1) BDNF: Brain derived neurotrophic is on chromosome 11and is 1,335 DNA bases long. In most cases, the 192nd letter in the gene is G, in some people, it is an A. Instead of valine, it is methionine. This causes a slightly different shape in protein. We get one chromosome 11 from dad with BDNF and one chromosome from mom with BDNF. That means we are either met-met, met-val, or val-val. Val-val are the most neurotic people. Metmet are the least neurotic people (met-val are in between). A change in the shape of protein, can affect depression. 2) Reelin gene is on chromosome 7, and is 12,000 DNA bases long. The gene is made up of 65 17 exons and is vital in brain development. This protein organizes the formation of the brain layers— directs the neurons where to grow and where to stop. A decrease in Reelin is found in people with schizophrenia, severe bipolar depression and autism. 3) Memory: Each neuron forms, on average, 70 synapses with other neurons. In the cell body, the nucleus will turn off the CREB gene (on chromosome 1), which will turn on other genes. The production of the other genes will stimulate the right synapse and strengthen the connection. The many genes necessary for learning and memory make up a machine called the Hebbosome. The hebbosome consists of 75 genes that work together. 18