Student Performance Objectives - for the lecture
1. State the functions of the nervous system.
2. Identify the 3 structural and the 3 functional types of neuron.
3. Given a diagram of a "typical" neuron, identify and state the function of:
a. axon, axolemma, axoplasm
b. cell membrane
e. myelin sheath
f. nodes of Ranvier, internodes
g. terminal axon fibers
h. Nissl bodies
i. Schwann cells
4. Explain the reason a unipolar neuron is said to have a single branched axon, and no dendrites.
5. Explain the formation of the myelin sheath in the peripheral and central nervous systems.
6. Explain the functions of the 5 different types of neuroglial cells.
7. Define each of the following terms as related to nervous tissue: irritability, conductivity.
8. Explain the importance of neurotubules, kinesin and dynein within the axon as related to the process of axon transport.
9. Explain the factors that cause the measurement of -70 mv as the potential across the cell membrane of a resting neuron.
10. Explain what is meant by local potentials developing along the dendrites and cyton of a neuron.
11. Explain an action potential in terms of the ion movements occurring across the neuronal cell membrane during depolarization and repolarization.
12. Explain the importance of membrane pumps in the continuous, lifelong ability of neurons to maintain the resting membrane potential (RMP).
13. Describe what a nerve impulse is.
14. Describe why nerve impulses travel at higher velocities in myelinated nerve fibers compared with unmyelinated nerve fibers.
15. Draw a labeled diagram of a chemical synapse.
16. Describe the transmission of a signal across an excitatory chemical synapse.
17. Explain the importance of neurotransmitter breakdown soon after synaptic transmission.
18. Explain the difference between an excitatory and inhibitory synapse on the basis of the functioning of the receptor on the postsynaptic membrane.
19. Explain how the nervous system codes for the quality and intensity of stimuli.
20. Explain the difference between a convergent and divergent neuronal circuit.
21. Distinguish between the central nervous system (CNS), the peripheral nervous system (PNS), and the autonomic nervous system (ANS).
Student Required Nervous System Items- for Laboratory Practical Examinations (items will be added or removed at your laboratory instructor's discretion). For each item, identify its position in a neuron model or on a microscopic slide of a neuron and indicate its function.
Properties - irritability and conductivity
A. Properties and Functions of the Nervous System
a. Irritability refers to the ability of neurons (cells of the nervous system) to detect and to respond to a stimulus.
b. Conductivity refers to the ability of neurons to transmit signals from one neuron to other neurons and from a neuron to muscles and glands.
a. Provide sensory awareness through electrochemical input to the central nervous system (CNS) from peripheral receptors. The word "peripheral" refers to parts of the body (e.g., the skin) outside the CNS (which is defined as the brain and the spinal cord).
b. Provide motor responses to sensory input: e.g., reflex muscular movements, voluntary muscular movements and glandular secretions.
c. Analysis of information brought into the CNS or analysis of thoughts generated within the CNS. Analysis in its highest form occurs in the brain and can result in a long delay between a sensory input and a motor response. E.g., one may respond to an insult years after the insult was delivered, or we may solve a problem weeks or months after initially becoming aware of the problem.
d. Memory - the ability to recall and integrate previous experiences into the analysis of information.
B. Nervous System Organization
1. The nervous system is broadly organized into the central nervous system (CNS) - brain and spinal cord, and the peripheral nervous system (PNS) - the 12 pairs of cranial nerves and 31 pairs of spinal nerves.
2. Other broad, functional divisions of the nervous system include the somatic nervous system (SNS) and the antonomic nervous system (ANS).
a. The SNS includes all neural pathways involved in the conscious sensing of stimuli (e.g., sights, sounds, touch, taste, odor) and the responses to those stimuli through the neural connections to the skeletal muscles.
b. The ANS includes all neural pathways involved in the innervation and control of the smooth muscles of the body's internal organs (e.g., blood vessels, digestive organs like the small intestine, reproductive organs like the uterus in females or sperm ducts in males) and cardiac muscle (found only in the heart).
3. At the cellular level of organization, the nervous system is based on the fundamental cellular unit - the neuron. It is estimated that there are about 1 trillion neurons in the nervous system. These highly irregularly shaped cells possess the nervous system's basic properties - irritability and conductivity.
4. Also at the cellular level are the specialized connective tissue cells of the nervous system - the neuroglia. There are at least 10 neuroglial cells for every one neuron in the nervous system. They come in different types each performing different functions that serve the activities of the neurons:
a. Schwann cells - synthesize myelin for the nerve fibers of the PNS.
b. Oligodendrocytes - synthesize myelin for the nerve tracts of the CNS.
c. Astrocytes - form structurally supportive and protective barriers around the neurons shielding them from direct contact with substances carried in the blood. Astrocytes form the basis of the blood-brain barrier and help regulate the chemical composition of the interstitial fluid directly bathing the neurons. They appear to communicate with neurons electrochemically and through their secretion of neuronal growth factors.
d. Microglia - protect neurons from microbes and can remove unwanted material (dead cells) from nervous tissue by phagocytosis.
e. Ependyma - cells lining the brains cavities (ventricles) that secrete and help circulate cerebrospinal fluid.
3. Connective Tissues associated with the Nerves composing the PNS:
a. Each nerve fiber (axon) of the PNS is surrounded by Schwann cells (and possibly a myelin sheath) surrounded by a thin layer of connective tissue, the endoneurium.
b. The nerve fibers making up nerves are arranged in groups called fascicles, with each fascicle surrounded by a slightly thicker layer of connective tissue, the perineurium.
c. All the fascicles of the nerve are surrounded by a thicker layer of connective tissue, the epineurium.
C. Neuron Organization
1. Functional Cell Types
a. Sensory (afferent) neurons - conduct nerve impulses into the CNS from peripheral receptors connected to the body surface (skin), major sense organs (e.g., eyes), and internal organs (e.g., pressure receptors in large arteries).
b. Motor (efferent) neurons - conduct nerve impulses from the CNS to peripheral effectors (e.g., skeletal muscles, smooth muscles, cardiac muscle, glandular tissue).
c. Association neurons (interneurons) - these neurons are found only in the CNS and conduct nerve impulses among themselves as part of the analysis and memory functions of the nervous system. They are the basis for the delay in response between an incoming sensory signal and an outgoing motor response. Association neurons make up as many as 90% of the neurons of the nervous system.
2. Structural Cell Types
a. Multipolar neurons - these are the most commonly observed type of neuron possessing many dendrites and a single axon. Most association neurons are multipolar.
b. Bipolar neurons - possess a single dendrite and a single axon. They are found in specialized locations associated with the delivery of sensory signals into the CNS - they are found in the olfactory epithelium of the nasal passages, the eye's retina, and in the inner ear.
c. Unipolar neurons - possess a single branched axon. They are the afferent neurons that bring sensory information into the spinal cord. Their cytons lie in the dorsal root ganglia and one of their axonal branches extends all the way out to a peripheral receptor. The other axonal branch extends into the dorsal horn of gray matter in the spinal cord. Both branches of a unipolar neuron's axon possess a myelin sheath.
3. Neuronal Organelles
a. The cyton or cell body of a neuron has most of the organelles seen in other cells including a nucleus, cell membrane, endoplasmic reticulum, Golgi, mitochondria, lysosomes and a cytoskeleton. However many of these organelles are modified to perform specialized functions and these will be emphasized below. One organelle lacking from neurons is the centriole apparently due to the inability of mature neurons to undergo mitosis. However some regions of the brain (notably the hippocampus) contain stem cells capable of producing new neurons by mitosis of these stem cells.
b. Nissl bodies - these were noted by early microscopists as deeply staining portions of the neuronal cyton (cell body). They are masses of rough endoplasmic reticulum involved in the synthesis of neuronal proteins. They occur in clumps that are bounded from the rest of the cytoplasm by neurofibrils - portions of the cytoplasmic cytoskeleton. Although mature neurons don't divide they are extremely metabolically active, as evidenced by the amount of Nissl substance they contain. It is easy to understand this in that the protein synthesis occurring in the cyton must supply the cyton itself with needed materials and also the long neuronal fibers that extend outward from the cyton.
c. Dendrites - extensions of the cyton that are generally short and numerous. They possess many synapses on their surface and conduct signals, emanating from other neurons, into the cyton. Dendrites, like the cyton, have no myelin sheath.
d. Axon - a single extension of the cyton arising from a slightly swollen area on the cyton called the axon hillock. The axon may vary in length from a few millimeters to a meter and carries nerve impulses away from the cyton toward other neurons, muscles or glands. Its membrane is called the axolemma and its contents are referred to as axoplasm.
(1) Axons of the PNS have a cellular covering of neuroglial cells - the Schwann cell sheath or neurilemma. If an axon is myelinated, the Schwann cell wraps itself around the axon, as much as 100 times, with each Schwann cell sequentially occupying an adjacent portion of the length of the axon. The tight Schwann cell wrappings, encircling the axon, are called the myelin sheath. The myelin sheath speeds up nerve impulse conduction along the axon. Areas covered by myelin are called internodes. Areas between Schwann cell- wrapped regions possess no myelin and are called Nodes of Ranvier. Unmyelinated axons in the PNS are still covered by Schwann cells, just without the multiple coils of membranous wrapping.
(2) Axons in the CNS may also have a myelin sheath but it forms from a different type of neuroglial cell than the Schwann cell of the PNS. The oligodendrocyte forms myelin sheaths in the CNS. It is believed that oligodendrocytes do not support regeneration of neurons, whereas Schwann cells do: this may be the reason that neuronal regeneration after damage is possible in the PNS (peripheral nerves), but is not commonly observed in the brain or spinal cord.
(2) Axons contain components of the cytoskeleton called neurotubules that serve as guidewires for the transport of organelles and chemicals from the cyton to the axon termination areas (anterograde transport) and from these terminal areas back to the cyton (retrograde transport). This overall process of movement of materials within the axon is called axon transport or axon flow. The power for this movement along the neurotubules is based on the activity of two motor proteins: kinesin powers anterograde movements and dynein powers retrograde movements.
(3) Each axon ends by forming tiny branches that have little swellings called synaptic knobs that form synapses with other neurons, muscle fibers or the cells of glands.
4. Neuronal bioelectrical effects
a. Sodium-Potassium Pump Action: a pump (called the sodium-potassium pump) in the cell membrane of a neuron uses the energy of ATP to pump potassium ions into the neuron and pump sodium ions out of the neuron. Chloride ions follow sodium and phosphates and negatively charged intracellular proteins tend to pair up with potassium. So, neurons are bathed in a sodium chloride solution on the outside and a potassium phosphate solution on the inside. Other ions are present and are important for certain activities, but these ions are most important for the membrane potentials. For each ATP molecule utilized, the sodium-potassium pump pulls 2 potassium ions into the cell and throws 3 sodium ions out of the cell.
b. Permeability of the cell membrane: the cell membrane permits the diffusion of relatively large amounts of potassium ions out of the cell and only a small amount of sodium ions into the cell. These diffusive movements are simply due to these ions moving down their concentration gradients after their active transport by the sodium-potassium pump..
c. Development of the Resting Potential:
The net charge on either side of the neuronal cell membrane is called the resting potential and is experimentally measured as about -70 millivolts (as measured from the inside where it is negative). This resting membrane potential (RMP) is due mainly to the the outward diffusion of potassium ions that result in a net positive charge developing on the outside of the cell membrane (potassium carries a single positive electrical charge) and a net negative charge on the inside of the cell membrane (due to the negative phosphate ions and proteins left inside when potassium diffused out of the cell). The permeability properties of the membrane do not allow phosphates or proteins to follow potassium when it diffuses out of the cell. If the outward diffusion of potassium ions were the only influence on the RMP, it would be about -90 mv. But there are 2 other influences:
(1) The unequal pumping action of the sodium-potassium pump: the pump brings only 2 positively charged potassium ions into the cell for each 3 positively charged sodium ions it ejects. The result is that the pump tends to make the RMP about -3mv lower than would be if the pump were not working. So if the outward diffusion of potassium and the sodium-potassium pump were the only factors at work in the establishment of the RMP, then the RMP value would be about -93 mv.
(2) Inward diffusion of positively charged sodium ions: some small amount sodium ions do diffuse into the cell and their positive charges neutralize some of the negative charges (left behind after potassium diffused out) bringing -90 mv to a less negative value. This effect of sodium is not as strong as might be expected because some negatively charged chloride ions accompany sodium when it diffuses into the neuron. So the net result of potassium diffusing out of the neuron, sodium and chloride diffusing into the neuron, and the action of the sodium-potassium pump is -70 mv.
d. Local potentials, action potentials, and the generation of a nerve impulse (1) Local potentials: The dendrites and the cyton of a single neuron in the central nervous system may have as many as 10,000 synapses on its combined surface area. A signal arriving at any one of those synapses may be stimulatory or inhibitory. Stimulatory means that the signal opens a ligand-gated channel (the neurotransmitter is the ligand that opens the gate) allowing sodium ions to enter the neuron. Inhibitory means that the signal opens a ligand-gated channel allowing potassium ions to leave the neuron. So, in every millisecond of existence in the nervous system, tens of thousands of signals influence the electrical charge on the dendrites and cyton of every neuron. These are referred to as local potentials. The net result of all the stimulatory and inhibitory signals (local potentials), each based on either stimulatory or inhibitory neurotransmitters attaching to the neuronal cell membrane, reaches the area of the axon hillock - the area of the cyton where the axon begins. This region is the first part of the neuron to possess voltage-gated ion channels (not the ligand-gated channels of the dendrites and cyton). If the signal is beyond the threshold value, meaning that the RMP has been changed from -70 to about -55 mv, then an action potential occurs.
(2) Action Potentials:
An action potential occurs when a voltage-gated ion channel opens and positively charged sodium ions diffuse into the axon changing the membrane potential from -70 to zero and even higher, often reaching +35 mv. We say that the membrane has been depolarized at that spot. It occurs in about 1/2 of a millisecond. Then the sodium gate closes and the usual outward diffusion of potassium occurs and the membrane potential returns to the resting potential of -70 and may go lower to -73 as there is often a temporary overshoot in outward diffusion of potassium. This return to the RMP is called repolarization. Repolarization takes about 1/2 of a millisecond. So an action potential is a depolarization followed by a repolarization and takes a total of about 1 millisecond.
(3) Nerve Impulses (signals):
When an action potential occurs at or near the axon hillock, the next area of the axon, just distal to the axon hillock, now goes through its own action potential. And then the area next to that one has an action potential and so on down the axon all the way to the axon terminals with no reduction in the intensity of the action potentials. The reason for this propagation of the action potential is that as sodium ions diffuse into the axon during the depolarization portion of the first action potential near the axon hillock, some of these sodium ions diffuse over to the next (adjacent) part of the axon and open the voltage-gated ion channels that are found there (and all along the axon). The stimulation of the voltage-gated ion channel then lets sodium ions enter, followed by potassium ions exiting and we have just generated a new action potential - sodium diffusing in followed by potassium diffusing out. And the process continues all the way down the length of the axon. So we see that what we call a nerve impulse, or bioelectrical signal, is a series of action potentials occurring sequentially down the length of the axon.
e. Nerve impulse propagation down unmyelinated and myelinated fibers
(1) The nerve impulse moves down unmyelinated nerve fibers slowly with each region of the axon going through depolarization and repolarization cycles utilizing voltage-gated sodium channels.
In this process, regions only fractions of a millimeter apart must each depolarize and repolarize as the signal is propagated. The result is a nerve impulse that travels at a rate of only about 2 meters/sec (about 4 miles per hour).
(2) The nerve impulse moving down a myelinated nerve fiber moves at much higher velocity - at between 100 and 120 meters/sec (about 220 - 265 miles/hour). The reason is what is called saltatory conduction: the points of depolarization and repolarization are not every adjacent spot on the axon, but only at nodes of Ranvier which are about 1 mm apart along the length of the axon.http://www.brainviews.com/abFiles/AniSalt.htm When sodium enters at one node of Ranvier during depolarization, it rapidly diffuses, inside the neuron, to the next node of Ranvier where it opens the voltage-gated sodium channel and a new depolarization-repolarization cycle occurs. So the impulse jumps along the axon from one node of Ranvier to the next (like a smooth, flat stone skipping across the water of a smooth lake; saltation means jumping along).
1. In general, synapses are points of communication between neurons. The space separating one neuron from the next one, the synaptic cleft, is only about 20-40 millimicrons in width. The majority of synapses in the nervous system are chemical synapses that operate through the release of neurotransmitters from the presynaptic neuron that stimulate or inhibit the postsynaptic neuron. However, about 5% of synapses are electrical synapses involving gap junctions that permit direct flow of ions from one cell into the next. These electrical synapses allow more rapid communication between cells.
2. Overall Structure - The presynaptic neuron of chemical synapses possesses a synaptic knob filled with synaptic vesicles attached to the cytoskeleton that are moved into and out of position to discharge their neurotransmitters through the presynaptic membrane into the synaptic cleft. The postsynaptic neuron possesses proteins on its postsynaptic membrane which serve as receptors for ligand-gated channels to permit movements of ions into and out of the postsynaptic membrane.
3. Calcium's Role:
An electrical signal traveling down a nerve fiber reaches the axon terminal and causes the opening of voltage-gated calcium channels permitting diffusion of calcium ions from the surrounding fluid to enter the synaptic knob. The electrical signal itself ends. The calcium that enters the synaptic knob causes the synaptic vesicles already positioned on the presynaptic membrane to discharge their content of neurotransmitters into the synaptic cleft. With continued electrical signaling and continued entry of calcium ions into the presynaptic neuron, discharged synaptic vesicles move off the presynaptic membrane and new "loaded" synaptic vesicles are moved into position as they slide along the cellular cytoskeleton into position on the presynaptic membrane.
4. Role of Receptor Sites: the neurotransmitter diffuses across the synaptic cleft and attaches to receptors on the postsynaptic membrane. The receptors open ligand-gated channels and ions diffuse into and/or out of the postsynaptic neuron depending on the nature of the neurotransmitter and the nature of the receptor.
5. Neurotransmitter and receptor site variations:
a. Neurotransmitters: over 100 chemicals have been identified acting as neurotransmitters. Acetylcholine was discussed in the muscular system chapter and also operates in many regions of the brain in both excitatory and inhibitory capacities. Also identified are such small molecules as excitatory amino acids and inhibitory amino acids. Another group of small chemicals are also found called monoamines such as epinephrine, norepinephrine, dopamine, histamine and serotonin. There are also a group of large molecules acting as neurotransmitters - the neuropeptides, such as endorphins and enkephalins.
b. Receptors: Postsynaptic membrane receptors are highly varied in their responsiveness to neurotransmitters. They determine the ultimate effect of the neurotransmitter. For example, acetylcholine stimulates skeletal muscle but inhibits cardiac muscle because the receptor in skeletal muscle permits ion movements that depolarize the postsynaptic membrane, while the receptor in cardiac muscle permits ion movements that hyperpolarize the postsynaptic membrane (meaning that it becomes even more positive on the outside and more negative on the inside making it less likely to depolarize).
6. Operation of an excitatory synapse that utilizes acetylcholine as the neurotransmitter:
After release of acetylcholine (Ach) from the presynaptic membrane and its diffusion across the synaptic cleft, it attaches to Ach receptors on the postsynaptic membrane. This attachment opens ligand-gated channels in the postsynaptic membrane and sodium and potassium ions briefly diffuse through the membrane - sodium ions diffuse in and then potassium ions diffuse out, both through the postsynaptic membrane. The inward diffusion of sodium ions depolarizes the membrane. If the effect of this local potential at the synapse is strong enough to cause the membrane potential at the region of the axon hillock of the postsynaptic neuron to reach the threshold value (about -55 mv), then the axon of the postsynaptic neuron will fire a nerve impulse. Cholinesterase found in the synaptic cleft breaks down Ach into acetic acid and choline, neither of which is capable of attaching to receptor sites. Choline is reabsorbed by the presynaptic membrane and utilized to synthesize more Ach. Cholinesterase inhibitors prevent the breakdown of Ach and result in spastic paralysis; they are the basis for many insecticides.
7. Operation of inhibitory synapses: some inhibitory synapses result in the opening of ligand-gated channels that permit potassium to leave the cell; others open channels that permit chloride to enter the cell. In either case, the result is a hyperpolarization of the membrane (opposite of depolarization) that makes subsequent depolarization less likely to occur.
E. Neuronal Integration
1. In general: Neuronal integration is a way of saying "thinking" in that it involves manipulating (processing) information, recalling facts that have been stored, and making decisions.
2. The synapse is of prime importance for neural integration. Whether or not a neuron fires depends on the sum of the excitatory and inhibitory postsynaptic potentials that impinge on the dendrites and cyton of the neuron in question.
3. Neuronal Coding: Understanding the quality of a stimulus and its intensity is dependent on neuronal coding. Quality depends on which neurons are stimulated which results in particular areas of the brain being signaled. There are cells in the eye (called cones) that specifically respond to wavelengths of light corresponding to the color red and these cells specifically signal portions of the cerebral cortex that then cause us to see the color red. How red or the intensity of the color is coded by the frequency of impulses (impulses/sec) reaching the brain: the more intense the color or the more intense any stimulus is, the greater the number of impulses reaching the brain per second.
4. Neuronal circuitry:
Neurons work in groups called pools that can consist of hundreds, thousands or millions of neurons linked through synapses. They are functionally connected through several types of circuits. In convergent circuits, many neurons send impulses toward one or a few neurons from which the "decision" to fire or not to fire emanates. In divergent circuits impulses travel out from a few neurons to many resulting in widespread responses to stimuli: this is common in the sympathetic branch of the ANS where observing danger can result in changes in many parts of the body - heart beat, breathing, sweating to name a few. Reberverating circuits result in neuronal interactions repeating as in rhythmic patterns of breathing or in continuing to think about an issue - short term memory.
5. Facilitating synaptic transmission may be a way of partially explaining memory. If memory is a specific pathway through the cerebral cortex involving a particular pattern of synapses, then allowing those synapses to fire more easily will allow that particular pathway to fire more easily as a whole. The result is that whatever that pathway signifies, comes to mind more easily.
F. Drug Effects on Neurons - the synapse is vulnerable to many drugs. The following examples are representative of the many substances affecting the nervous system's chemical synapses.
1. Substances that Enhance Signal Transmission across the Synapse
a. Prozac (fluoxetine) - Prozac acts as an antidepressant because it blocks presynaptic membrane reabsorption (reuptake) of the monoamine neurotransmitter, dopamine, so that its mood-elevating effects are prolonged. Prozac is frequently referred to as a serotonin reuptake inhibitor.
b. MAO inhibitors - Monoamine oxidase (MAO) is an enzyme that works within the presynaptic neuron to breakdown reabsorbed monoamine neurotransmitters, like serotonin. Drugs that inhibit the action of MAO (the MAO inhibitors) can elevate mood. This is because they increase the quantity of monoamines in the synapses as they reduce the rate of breakdown of the monoamines.
c. Cocaine - cocaine is a dopamine reuptake inhibitor. Since dopamine is a neurotransmitter associated with providing feelings of pleasure, use of cocaine increases pleasurable feelings. The downside of cocaine use is the development of dependence on it for any feelings of pleasure. With continued use of cocaine, the neurons cannot produce enough dopamine to produce pleasurable sensations under non-drug-use conditions. One must use the drug for the small amount of dopamine that is made to stay long enough to provide one with pleasurable sensations. The underlying problem for the neurons is that when cocaine prevents dopamine reuptake, the dopamine diffuses away from the neurons and is degraded by other cells. Then, the presynaptic neurons must re-synthesize dopamine and this process does not occur rapidly enough to provide a normal level of pleasurable sensations.
d. Caffeine enhances signal transmission across the synapse because it structurally resembles the CNS inhibitory neurotransmitter, adenosine. The result of drinking coffee or consuming other foods containing caffeine is that the caffeine binds to adenosine receptor sites but does not cause inhibition of nervous system activity (sleepiness).
2. Substances that Stimulate Transmission across the Synapse
a. Amphetamines stimulate dopamine and norepinephrine receptors because the amphetamine molecule has enough of a molecular resemblance to dopamine and norepinephrine.
The following animations summarize many of the concepts covered in this unit:
Biomedical Terminology: Define each term.
ligand gated channels
nodes of Ranvier, internodes
resting membrane potential
terminal axon fibers
voltage-gated sodium channels