Author: Dr. T. Hoekman thoekman@mun.ca ----- Last modified August 31, 2004
The axon is often a very long cell process, in some cells being 5-10,000 times as long as the cell body is wide. This presents some difficulties in resource management for the cell, since the genetic material and the bulk of the synthetic material is located in or close to the nucleus. Nerve cells have evolved a specialized axonal transport process to facilitate the physical movment of cell products to the terminal (anterograde transport). Similarly the terminal may absorb substances which are important as metabolic precursors or as regulators of cell processes which are transported back to the cell body (retrograde transport). The transported substances may have profound effects, nerves exert 'trophic effects' on many cells they contact quite distinct from the neuro-transmitter/electrical activation functional axis. In addition substances take up by nerves from other cells are critically important in their homing in and forming appropriate connections during development and appear to modulate many of their properties during their entire life.
The neuron normally demonstrates polarity or functional uni-directional transmission of action potentials. Under 'physiological' coditions an ALL-OR-NONE action potential will be propagated from the cell body/dendrite end to the axon terminal end (including the collaterals). Physically there is no reason why propagation in the opposite direction can not occur, but the specialized properties of the dendrites and the nerve terminals make this event highly unlikely.
The synapse represents a specialized structural and functional relationship between the nerve terminal, and an adjacent cell. Their plasma membranes are not physically continous, but an action potential in the presynaptic cell will result in an electrical event in the membrane of the post-synaptic cell. In the vertabrate nervous system the synaptic transmission event is predominantly mediated via chemical neurotransmitters, and is strictly uni-directional. More rarely there are electrical synapses which are not so unambiguouly uni-directional in their transmission properties. When a nerve-nerve synapse occurs, a nerve terminal will form a contact with a dendritic process. In chemically mediated synapses when the pre-synaptic action potential occurs, a small amount of neurotransmitter is released and diffuses across the synaptic cleft to interact with postsynaptic receptors. These receptors are coupled to an ionic conductance channel, and their binding will result in activation of a specific ionic conductance, which in turn leads to a change in trans-membrane potential. The dendrites appear to have very sparse distribution of the voltage-activated channels necessary for action potential generation, but exhibit excellent cable properties thus allowing the synaptic transmission event to be conducted decrementally to regions like the axon hillock which are more generously endowed. If the synaptic event is depolarizing and it exceeds the threshold at this site, an action potential will be initiated to propagate down the axon.
Neurons are organized in the human body with the vast majority existing entirely in the brain and spinal cord, which is known as the Central Nervous System. The remainder form the bridge between the CNS and the tissues, organs and cells outside the CNS, and are designated the Peripheral Nervous System. No part of a CNS neuron is outside the brain or spinal cord; all or part of a Peripheral neuron is outside.
From a functional point of view there are three classes of neurons:
1. Afferent Neurons communicate information from the the periphery to the CNS. Afferent nerve cells typically show a variation on the basic structural theme. The cell body is located at some point midway between a specialized sensory process, and the nerve terminal making the synaptic connection with the rest of the CNS.
2. Efferent Neurons communicate information from the CNS to effector organs (Muscles, glands, etc.)
3. Interneurons make connections between Afferent and Efferent Neurons; they constitute 99% of the neurons in the body.
Like all successful actors, the neurons have a supporting cast; in the CNS there are approximately 10 glial cells for every nerve cell. Glial cells DO NOT form synapses or conduct action potentials in spite of the fact that there is evidence that they may become passively polarized in response to nearby neurons. Their range of function is complex and not well understood; They form a physical matrix which supports the neurons, probably providing a conduit for nutrients and a sink for removal and inactivation of metabolic products. They act as generalized 'maintaince' cells clearing the physical debris by phagocytosis and maintaining a healthy milieu for the neuron. It is suggested they act as electrical insulators, reducing the possibility of inappropriate cross-talk between neurons.
There are 5 broad types of glial cells which have been described:
Astrocytes - Star-shaped, found throughout the brain and spinal cord. Their processes surround neurons often ending on the walls of blood vessels. In addition to their function as a mechanical matrix they probably serve metabolic and nutritive functions consistent with their location and relationship between the vasculature and the neurons.
Ependymal cells - line the surfaces of the ventricles in the brain and the central canal of the spinal cord; function is not clear
Microglia - smallest cells in the CNS, have no obvious function until nervous tissue damage occurs. Then they enlarge and phagocytize debris.
Oligodendrocytes - found in brain and spinal cord, responsible for myelination of axons at these sites.
Schwann Cells - found in peripheral NS where they account for myelination of axons there.
The latter two types of glial cells are responsible for an important structural and functional modification of nerve cells the formation of myelin. In the periphery Schwann cells migrate around the axon laying down a double layer of plasma membrane with very little cytoplasm between them, and an infinitesimal layer of extracellular fluid in the space between succesive spirals of the encircling membrane. The result is the production of a thick layer of membrane lipid with exceptional insulating properties (MYELIN). The Schwann cells and oligodendrocytes align on the axon with very regular spacing producing regions of high insulation (and extremely high transmembrane resistance) with gaps (Nodes of Ranvier) at the junction between two encircling cells (every 1-2 mm) where the insulation is interrupted (and Rm is much lower).
Nerves displaying this pattern of myelination have a functional behaviour known as saltatory conduction. Because of the high effective transmembrane resistance produced by the myelin, current from an action potential will flow quite selelctively through the next node, depolarizing to threshold, and 'leap-frogging' over the intervening membrane. Because the 'passive' conduction does not involve channel state transitions it occurs more quickly than action potentials and as a result the overall conduction velocity as the action potential skips from node to node. This process is also metabolically conservative since Na+ influx and K+ efflux occur through a very small membrane area, net ion movement is very small, and the activity of the sodium pump after action potential activity is less than if the entire axon had been involved in the action potential process.
In the real physiological world there are two categories of action which can trigger an action potential in a nerve cell: 1) a sensory cell transduction event or 2) a synaptic transmission event.
Stimulus-response records of a pacinian corpuscle. The two traces represent the generator potentials recorded in the axon in response to the application of forces 50 msec in duration. On the top is the stimulus-response pattern of an intact pacinian corpuscle. The bottom trace is the stimulus-response pattern to stimulation of the distal tip of the axon after removal of the onionlike structure of the tip. The depolarizing generator potential is NOT dependent on the onionlike structure, but a property of the nerve tip.
Sustained Pacinian Corpuscle Electrical Response. Note the extremely phasic responses that occur only when the stimulus changes, e.g. at onset and termination. The pattern on the right, after removal of the onionlike structure is relatively tonic. That is the depolarization persists as long as the mechanical stimulus continues.
If we use as an example the Pacinian corpuscle, a sensory structure which mediates the sensation of pressure and vibration, some useful generalizations about the properties of sensory receptors can be made. With this receptor the tip of the afferent nerve is encased in a multi-layered onion-like structure. Pressure on this 'corpuscle' results in a depolarization at the first adjacent Node of Ranvier that is proportional to the applied pressure. When the threshold for an AP is exceeded it will propagate to the synaptic connections within the CNS. This sensitivity to mechanical deformation has been show to be a property of the nerve membrane at the core of the corpuscle. When distorted there is a generalized increase in the membrane conductance, but primarily an increase to Na+ which results in a driving toward its equilibrium potential (+55 mV) hence a depolarizing response. The membrane at the nodes of the axon IS NOT pressure sensitive. The nature of the 'onion' results in a 'phasic' receptor. When point pressure is applied, it deforms and deforms the nerve ending. However very quickly the viscous capsule 'flows' changing its shape and relieving the pressure on the ending, hence the effective stimulus rapidly dissipates. When the pressure point is removed there will again be a transient distortion as the shape returns to the starting point, and another brief effective mechanical stimulus. This receptor is a 'phasic' or rapidly adapting receptor; effectively an 'on-off' detector when the capsule is intact. If however the onion is peeled, and pressure is applied directly to the nerve ending we see a quite different phenomenon; the receptor now becomes a 'tonic' or slowly adapting receptor. That is when pressure is applied there will be a sustained generator potential as long as pressure is maintained. This results in the generation of a train of action potentials from the depolarized first Node of Ranvier. The larger the depolarization above threshold, the greater the frequency of repetition of the action potential train. This provides a quantitative coding of stimulus intensity as action potential frequency.