Nerve Conduction And Synaptic Integration
Nerve conduction
Action potential propagation is achieved by local current spread and is made
possible by the large safety factor in the generation of an action potential as
a consequence of the positive feedback of Na+ channel activation in
the rising phase of the nerve impulse (see Chapter 15). However, the use of
local current spread does set constraints, not only on the velocity of nerve
conduction; it also influences the fidelity of the signal being conducted. The
nervous system overcomes these difficulties by insulating nerve fibres above a
given diameter with myelin, which is periodically interrupted by the nodes of
Ranvier.
• In unmyelinated
axons an action potential at one site leads to depolarization of the
membrane immediately in front and theoretically behind it, although the
membrane at this site is in its refractory state and so the action potential is
only conducted in one direction (see Chapter 15). The current preferentially
passes across the membrane (because of the high internal resistance of the axoplasm)
and is greatest at the site closest to the action potential. However, while
nerve impulse conduction is feasible and accurate in unmyelinated axons,
especially in the very small diameter fibres where the internal axoplasmic
resistance is very high, it is nevertheless slow. Conduction velocity can
therefore be increased by either increasing the axon diameter (of which the
best example is the squid giant axon with a diameter of ∼1 mm) or
insulating the axon using a high-resistance substance such as the lipid-rich
myelin.
• Conduction
in myelinated fibres follows exactly the same sequence of events as in
unmyelinated fibres, but with a crucial difference: the advancing action
potential encounters a high-resistance low-capacitance structure in the form of
a nerve fibre wrapped in myelin. The depolarizing current therefore passes
along the axoplasm until it reaches a low-resistance node of Ranvier with
its high density of Na+ channels and an action potential is
generated at this site. The action potential therefore appears to be conducted
down the fibre, from node to node – a process termed saltatory conduction.
The advantage of myelination is that it allows for rapid conduction while
minimizing the metabolic demands on the cell. It also increases the packing
capacity of the nervous system, so that many fast-conducting fibres can be
accommodated in smaller nerves. As a result most axons over a certain diameter
(∼1 μm) are myelinated.
Disturbances in nerve conduction
are clinically seen when there is a disruption of the myelin sheath, e.g. in
the peripheral nervous system (PNS) in inflammatory demyelinating neuropathies
such as the Guillain–Barré syndrome and in the central nervous
system (CNS) with multiple sclerosis (see Chapter 62). In both
conditions there is a loss of the myelin sheath, especially in the area
adjacent to the node of Ranvier, which exposes other ion channels, as well as
reducing the length of insulation along the axon. The result is that the
propagated action potential has to depolarize a greater area of axolemma, part
of which is not as excitable as the normal node of Ranvier because it contains
fewer Na+ channels. This leads to slowing of the action potential
propagation and, if the demyelination is severe enough, actually leads to an
attenuation of the propagated action potential to the point that it can no
longer be conducted – so-called conduction block.
Synaptic integration
Each central neurone receives many
hundreds of synapses and each input is integrated into a response by that
neurone, a process that involves the summation of inputs from many different
sites at any one time (spatial summation) as well as the summation of
one or several inputs over time (temporal summation).
Presynaptic
The presynaptic nerve terminal usually
contains one neurotransmitter, although the release of two or more transmitters
at a single presynaptic terminal has been described – a process termed cotransmission
(see Chapter 18). The amount of neurotransmitter released is dependent not
only on the degree to which the presynaptic terminal is depolarized, but also
the rate of neurotransmitter synthesis, the presence of inhibitory presynaptic
autoreceptors and presynaptic inputs from other neurones in the form of
axoaxonic synapses (see Chapter 18). These synapses are usually inhibitory
(presynaptic inhibition) and are more common in sensory path- ways (see, for
example, Chapter 32).
Postsynaptic
The released neurotransmitter acts
on a specific protein or receptor in the postsynaptic membrane and in
certain synapses on presynaptic autoreceptors (see Chapter 18). When
this binding leads to an opening of ion channels with a cation influx in the
postsynaptic process with depolarization, the synapse is said to be excitatory,
while those ion channels that allow postsynaptic anion influx or cation efflux
with hyperpolarization are termed inhibitory.
• Excitatory
postsynaptic potentials (EPSPs)
are the depolarizations recorded in the postsynaptic cell to a given excitatory
synaptic input. The depolarizations associated with the EPSPs can go on to
induce action potentials if they are summated in either time or space. Spatial
summation involves the integration by the postsynaptic cell of several
EPSPs at different synapses with the summed depolarization being sufficient to
induce an action potential. Temporal summation, in contrast, involves
the summation of inputs in time such that each successive EPSP depolarizes the
membrane still further until the threshold for action potential generation is
reached.
• Inhibitory
postsynaptic potentials (IPSPs)
are hyperpolarizations of the postsynaptic membrane, usually as a result of an
influx of Cl− and an efflux of K+ through their
respective ion channels. IPSPs are very important in modulating the neurone’s
response to excitatory synaptic inputs (see figure). Therefore inhibitory syn-
apses tend to be found in strategically important sites on the neurone – the
proximal dendrite and soma – so that they can have profound effects on the
input from large parts of the dendritic tree. In addition, some neurones can
inhibit their own output by the use of axon collaterals and a local inhibitory
interneurone (feed-back inhibition), e.g. motor neurones and Renshaw
cells of the spinal cord (see Chapter 37).
More long-term modulations of
synaptic transmission are discussed in Chapters 40, 45 and 49, and in
some disorders of the nervous system (e.g. epilepsy, multiple sclerosis)
abnormal transmission of information may occur via non-synaptic mechanisms.
