PSM11K

Unit XI - Cellular Basis of the Nervous System

The nervous system functions in control, communication, and integration of the body. The nervous systems is made up of a central division (brain and cord) and a peripheral division (cranial and spinal nerves). Like all organ systems the nervous systems is composed of cells. There are three basic types of cells found in the system. These are the neurons, Schwann cells, and neuroglial cells.

A. Neurons - These are the functional and structural units of the nervous system. It is the neurons that conduct the action potentials. Neurons are extremely long lived, up to 100 years or more. This is necessary as they are amitotic and do not divide(an exception is the hippocampus region of the brain). They have a very high metabolic rate and must have a continuous supply of glucose and oxygen.

 

1. Structure - The neuron is one of the most highly specialized if all cells. Functionally, all neurons have three general regions. There is a receptive or input region, a conducting region that generates action potentials, and a secretory or output region that releases neurotransmitters. Anatomically, they consist of a cell body (perikaryon, soma), nucleus, and long appendages. The more specialized parts of a typical neuron are as follows.

a. Nissl bodies - These are condensations of the rough ER which form dark staining bodies. They are composed of RNA and protein. They function in protein synthesis. Neurons have the highest rate of protein synthesis of any cell in the body.

b. Neurofibrils - These are slender, rod-like structures which are composed of microtubules and microfilaments. They function in cell support and release of neurotransmitter.

c. Dendrites - These are highly branched cell processes. They, along with the cell body, represent receptive region of the neuron. Dendrites conduct signals toward the cell body. The signals are graded (local) potentials, not action potentials. Dendrites contain Nissl bodies.

d. Axons - These are processes that generate and conduct the action potential away from the cell body. They represent the conducting region of the neuron. They do not contain Nissl bodies.

(1) The first part of the axon is known as the initial segment and is connected to a special region of the cell body known as the axon hillock. The axon hillock contains neurofilaments and neurotubules that extend into the axon. It is at the hillock that the action potential is initiated.

(2) Axons may branch all along their length giving rise to collaterals.

(3) The terminations of the axon and all collaterals are a series of fine extensions known as telodendria. Each axon will usually have 10,000 or more telodendria. The telodendria expand at their tips to form synaptic knobs. These terminations represent the secretory component of the neuron as it is from here that neurotransmitter is released.

e. Myelin sheath - This a white envelope found surrounding the axons of many nerve cells. The substance that makes up the bulk of this sheath is a white lipid known as myelin. The origin of this sheath is different in the PNS and CNS.

(l) PNS formation - Here the sheath is formed by Schwann cells which wrap around the neuronal processes. Each cell folds around its process segment many times forming many layers of membrane. These membranes are very rich in myelin. Satellite cells are usually associated with Schwann cells and play a role in regulating the chemical environment and not myelination. Where adjacent Schwann cells meet there are small gaps which are known as the nodes of Ranvier. The nucleus and cytoplasm lie just beneath the outermost layer of membrane and form a "tube" around the myelin sheath known as the neurilemma. When an axon is cut the neurilemma forms a regeneration tube. This tube seems to secrete chemicals that attract the growing end of the axon and direct it towards its appropriate termination. This is why most peripheral nerve damage is repairable.

(2) CNS formation - In the central nervous system myelin sheaths are formed by a special kind of neuroglial cell known as an oligodendrocyte. As in the PNS, nodes of Ranvier exist. There is no neurilemma because each oligodendrocyte produces extensions that may myelinate up to 60 different processes. Therefore, repair of damaged neurons in the CNS is extremely limited.

(3) In both the CNS and PNS, only axons are myelinated. Dendrites are not myelinated.

2. Classification of neurons - There are two major ways in which neurons are classified. One is by means of the neurons function and the other is by means of the number process leaving the cell body.

a. Functional

(1) Motor neurons (efferent neurons) - These conduct impulses away from the CNS. Structurally, these are usually multipolar.

(2) Sensory neurons (afferent neurons) - These conduct impulses toward the CNS. Structurally, these are usually unipolar.

(3) Association (interneurons) - These are found within the CNS. They connect motor and sensory neurons together. They are usually multipolar. About 99% of all neurons in the body are classified as association.

b. Structural

(1) Multipolar - These have more than two major processes coming off of the cell body. They usually have many such processes. Most motor and interneurons are of this type.

(2) Bipolar - These have two major processes coming off of the cell body. They are often associated with the special senses such as vision and hearing.

(3) Unipolar - There is but a single major process coming off of the cell body. This process usually divides into two parts, a peripheral process (from a sense organ) and a central process (to the central nervous system. The peripheral process is not a dendrite in that (1) it is myelinated and (2) it conducts action potentials and not graded potentials. Most sensory neurons are of this type.

B. Neuroglial cells - These are supportive cells of the CNS. They outnumber the neurons about ten to one. They are of clinical interest because it is these cells that usually form tumors. There are four major types of neuroglial (glial) cells.

1. Astrocytes - These are the most numerous of the glial cells. Their name comes from the fact that they have long protoplasmic extensions giving them a star-like appearance. Astrocytes are known to have several important functions.

a. They metabolize glutamate and GABA, two important neurotransmitters.

b. They help maintain proper potassium levels in the region of the neurons by removing and sequestering any excess potassium from the extracellular fluid.

c. They play a role in embryology including the formation of certain brain parts and induction of the blood brain barrier. This barrier is formed by tight junctions between the endothelial cells of the capillaries in the brain. This retards the rapid movement of material from the circulation to the brain and makes the endothelium almost impermeable to water soluble substances.

d. They release numerous factors that promote the growth and healing of injured neurons.

e. They form scar tissue.

f. They play a role in the immune response by functioning as antigen presenting cells for lymphocytes.

2. Oligodendrocytes - Function to form myelin sheaths in the CNS.

3. Ependymal cells - These line the cavities of the CNS and are modified in certain regions to form CSF (cerebral spinal fluid).

4. Microgliocytes - These are small phagocytic cells derived from connective tissue. The play a role in destruction of dead tissue and defense against microorganisms. For these reasons they are considered to be part of the reticuloendothelial (RE) system.

C. Physiology of neurons - The operation of the nervous system is ultimately the operations of the neurons. As the functional units, the neurons ultimately are responsible for all of the activities that we associate with the nervous system.

1. Properties of the neuron

a. Neurons follow the all or none principle.

b. The resting membrane potential averages about -70 mv.

c. The initial response is an action potential. The secondary response is the release of a chemical (neurotransmitter) by the terminal filaments of the axon into the myoneural junction or a synapse.

d. The action potential is due to the opening of electrically gated ion channels at the threshold potential. The threshold potential is reached by graded potentials which are due to the opening of chemically gated sodium channels.

d. Saltatory conduction - This occurs in myelinated fibers. In this type of conduction, the action potential "skips" from node of Ranvier to node of Ranvier. The myelin sheath acts like an insulator. This skipping or saltatory conduction is much more rapid than continuous conduction of non-myelinated fibers.

e. Conduction velocity - There are two major factors which govern conduction velocity.

(l) Fiber diameter - The larger the diameter, the greater the velocity.

(2) Presence of myelin - Myelinated fibers conduct much faster than unmyelinated.

(3) Small, unmyelinated fibers conduct at about one meter per second. Large myelinated fibers conduct at around 120 meters per second.

f. Based upon degree of myelination and conduction velocity, neurons are placed into three different groups.

(1) Group A - Large diameter, heavily myelinated, and conduction from 15 to about 140 m/sec.

(2) Group B - Intermediate diameter, light myelination, and conduction velocity of 3 - 15 m/sec.

(3) Group C - Small diameter and unmyelinated. Conduct at about 1 m/sec.

 

3. Synapses - These are the junctions between two or more neurons. The neuron which conducts the impulse toward the synapse is said to be the presynaptic neuron. The neuron which conducts the impulse away from the synapse is said to be the postsynaptic neuron. There are two major types of synapses.

    1. Electrical - The presynaptic and postsynaptic membranes are in direct contact and connected to one another by gap junctions. This permits the direct transmission of action potentials from one neuron to the next. Electrical synapses are scarce in the adult and are found in brain regions responsible for stereotypical movements such as the movement of the eyes.

b. Chemical - There is a space between the membranes of the presynaptic and postsynaptic neurons. This space is termed the synaptic cleft. Transmission of the action potential across the cleft is by chemical means.

(1) Chemical transmission - Chemical substances termed neurotransmitters are released by the synaptic bulbs of the axons on the presynaptic neurons.

(a) Release of neurotransmitters is due to the opening of voltage regulated calcium gates which open during the action potential. This allows calcium to enter the neuron and the elevated levels of calcium promote the release of neurotransmitter into the synaptic cleft.

(b) These substances diffuse across the synaptic cleft and attach to the receptors on the membrane of the postsynaptic neuron causing depolarization (opening of sodium channels) or hyperpolarization (opening of potassium channels).

(c) Once transmission has occurred the effect of the neurotransmitter must be terminated. This is accomplished in one of three ways.

/1/ The neurotransmitter is broken down chemically.

/2/ Reabsorption by the presynaptic neuron where it is recycled or destroyed.

/3/ Diffusion of the transmitter out of the synapse.

(2) Neurotransmitters and Neuromodulators - Neurotransmitters are substances which are released by the presynaptic neuron on to the postsynaptic membrane. They may be either excitatory or inhibitory. Excitatory transmitters cause the postsynaptic neuron to depolarize while inhibitory neurotransmitters cause hyperpolarization. Hyperpolarization takes the membrane potential further away from threshold. Neuromodulators are substances released into the tissue fluid or into the CSF. They may alter the signaling of local or distant neurons either enhancing or diminishing their activity. Over 100 different substances are suspected to function as neurotransmitters or neuromodulators.. Most neurons produce only one transmitter type, but some neurons may produce several. The following list consists of those which have been firmly established as transmitters or modulators.

(a) Acetylcholine - Excitatory except in the ANS where it can be both excitatory and inhibitory.

(b) Biogenic amines - These consist of the catecholamines (dopamine, norepinephrine) and the indolamines (serotonin and histamine.

/1/ dopamine - excitatory

/2/ norepinephrine - excitatory or inhibitory

/3/ serotonin - inhibitory

/4/ histamine - excitatory

(c) amino acids

/1/ GABA (gama amino butyric acid) - inhibitory

/2/ glycine - inhibitory

/3/ glutamate - excitatory

(d) Nitric oxide (NO) - This is a gas (usually associated with air pollution) that is highly toxic at elevated levels, but has been discovered to be a major mediator of numerous physiological functions. One of these is that it functions as a neurotransmitter and may be very important in memory and learning.

(e) Carbon monoxide (CO) - Another toxic gas that has been found to function as a neurotransmitter in the brain.

(f) peptides

/1/ Endorphins (Endogenous morphine-like substances) - These modulate (reduce) pain perception.

/2/ Enkephalins - Inhibit pain by suppressing the release of substance P by means of presynpatic inhibition.

/3/ ACTH (adrenocorticotrophic hormone) - This may function in memory.

 

/4/ CCK-8 (cholecystokinin) - Depresses feeding behavior.

/5/ Angiotensin - This increases blood pressure, improves memory, and stimulates thirst.

/6/ Substance P - This is a mediator of pain signals.

4. Physiological properties of the synapse - The functioning of the nervous system is essentially the functioning of the synapses. In one sense, the nervous system is like a digital computer with information processing and storage being the function of different pathways. It is the synapses that determine these pathways and therefore are responsible for information coding and storage. The major properties of the synapses are presented below.

a. Synaptic delay - The fact that neurotransmitter must be released and diffuse across the cleft to the postsynaptic neuron requires time and therefore a delay always occurs at a synapse.

b. One-way conduction - A neuron will conduct an action potential in any direction. When the action potential reaches a synapse it can only proceed from axon to dendrite because only the axons contain neurotransmitter which is necessary for the crossing of the synapse.

c. EPSP and IPSP - These stand for excitatory postsynaptic potential and inhibitory postsynaptic potential respectively. These are graded or local potentials that will bring the post synaptic membrane closer to or further from the threshold point of action potential generation. The origin of these local potentials are the excitatory and inhibitory neurotransmitters released by the presynaptic neurons. A postsynaptic neuron with an EPSP is closer to threshold and much more like to fire that one without such a local potential. A postsynaptic neuron with an IPSP is further away from threshold and therefore much less likely to fire. from the threshold value and less likely to fire

d. Summation - This is the adding up of EPSPs and IPSPs.It is a very important property because it is one method in which neurons which are primarily binary (on-off) can response to levels of stimulus. There are two types.

(1) Spatial - Here several presynaptic neurons fire more or less simultaneously. Each firing released neurotransmitter which contribute an EPSP or an IPSP. The summation of these EPSPs and IPSPs will determine whether the post synaptic neuron generates an action potential. Note that it is possible for presynaptic neurons to release both inhibitory and excitatory neurotransmitters and consequently the postsynaptic neuron functions to "integrate" all of the various signals being received from the presynaptic neurons.

(2) Temporal - This is summation in time. Several rapid firings of a presynaptic neuron cause neurotransmitter to accumulate and EPSPs or IPSPs to develop on the postsynaptic neuron.

e. Facilitation - This is the lowering of the resting potential of the postsynaptic neuron making it more excitable. This is basically the mechanism of summation of excitatory neurotransmitters. Repeated firings of one neuron or the combined firing of several generate small local potentials (EPSPs) that move the postsynaptic membrane towards threshold. The closer the membrane is to threshold, the more excitable it is, i.e., the less it takes to cause it to depolarize.

f. Inhibition - This is the opposite of facilitation. Presynaptic neurons release inhibitory transmitters that result in hyperpolarization of the membrane, taking it further from the threshold value and therefore making it much more difficult to fire.

g. Synaptic potentiation - This represents an increase in the size of the EPSP brought about by repeated use of a synapse. It is apparently due to an increase in the amount of neurotransmitter being released by the presynaptic neuron. This in turn leads to a larger EPSP which is much more likely to reach threshold. There are two types of potentiation.

(1) Tetanic - The potentiation occurs only during the repeated firings of the presynaptic neuron.

(2) Post-tetanic - This is potentiation that remains after the stimulus ends.

Potentiation represents a special case of facilitation in which certain pathways preferentially fire. It therefore represents a mechanism for learning and recall.

h. Convergence and divergence - At a typical synapse in the central nervous system thousands of neurons meet. Sometimes there are relatively few presynaptic neurons and many postsynaptic neurons. This is divergence. Here an impulse from a single presynaptic pathway can cause a large number of postsynaptic neurons to fire, thereby spreading the impulse to many parts of the nervous system. The opposite of this phenomena is convergence whereby many presynaptic neurons approach a synapse and a relatively few postsynaptic neurons exit the synapse.

i. Presynaptic inhibition and facilitation - This is the process by which an inhibitory or excitatory neuron

makes contact with the presynaptic neuron terminal filaments of an excitatory neuron and reduces or

increases the amount of neurotransmitter which it releases. This results in a smaller or larger EPSP.

This also represents a special synapse known as an axoaxonic synapse.

    1. Fatigue - This represents exhaustion of the neurotransmitter from a presynaptic neuron. A neuron

can be fired many times with virtually no lost of efficiency, but eventually the neurotransmitter may

become exhausted and consequently all effects on the postsynaptic neuron are lost. This represents

neural fatigue and the fatigued synapse will not again be functional until the presynaptic neurons have had sufficient rest to allow them to regenerate adequate supplies of neurotransmitter.