Neuroscience
Online
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Section I:
Cellular and Molecular Neurobiology
6. Synaptic Transmission in the Central Nervous System
Part 2 of 2
John H. Byrne, Ph.D.
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Temporal
and Spatial Summation
If the amplitude of the postsynaptic potential is only 1 mV, how can an action
potential in the motor neuron be triggered and the reflex function? Note that
a 1-mV EPSP is unlikely to be sufficient to drive the membrane potential of the
motor neuron to threshold to fire a spike. If there is no spike, there will be
no contraction of the muscle. The answer is that the stretch of the muscle fires
multiple action potentials in many different stretch receptors. In fact, the greater
the stretch, the greater is the probability of activating more stretch receptors.
This process is referred to as recruitment.
Therefore, multiple 1A afferents will converge onto the spinal motor neuron and
participate in its activation. This is not the whole answer, however. Recall that
the greater the intensity of the stimulus, the greater is the number of action
potentials elicited in a sensory receptor. The greater the stretch, the greater
the number of action potentials elicited in a single sensory neuron and the greater
number of EPSPs produced in the motor neuron from that train of action potentials
in the sensory cell. The processes by which the multiple EPSPs from presynaptic
neurons summate over space and time are called temporal and spatial summation.
Temporal summation. A
single action potential in sensory neuron 1 produces a 1-mV EPSP in the motor
neuron. Now consider the consequences of firing two action potentials in quick
succession (See figure above). Two EPPs are elicited, the second of which summates
on the falling edge of the first. As a result of two action potentials, a summated
potential about 2 mV in amplitude occurs. If there were three presynaptic action
potentials, and they occurred rapidly enough, the total potential would be about
3 mV, and so forth. Temporal summation is strictly a passive property of nerve
cells. Special ionic conductive mechanisms are not needed to explain it. The
potentials summate because of the passive properties of the nerve cell membrane,
specifically the ability of membranes to store charge. The membrane temporarily
stores the charge of the first PSP and then the charge from the second PSP is
added to it to produce a potential twice as large at first. This process of
temporal summation is very much dependent upon the duration of the synaptic
potential. The temporal summation occurs when the presynaptic action potentials
occur in quick succession. The time frame is dependent upon the passive properties
of the membrane, specifically the time constant.
Spatial summation. Now
consider a motor neuron that receives two inputs. An action potential produced
in sensory neuron 1 produces a 1-mV EPSP and a single action potential in sensory
neuron 2 also produces a 1-mV EPSP. If action potentials are produced simultaneously
in sensory neuron 1 and in sensory neuron 2, the EPSPs summate to produce a
summated EPSP which is twice that of the individual EPSPs. Spatial summation
in nerve cells occurs because of the space constant, the ability of a charge
produced in one region of the cell to spread to other regions of the cell.
IPSPs
Whether a neuron fires in response to a synaptic input is dependent upon how many
action potentials are being fired in any one afferent input, as well as how many
individual afferent pathways are activated.
The decision to fire also depends on the presence of inhibitory synaptic inputs.
Artificially depolarizing the interneuron to initiate an action potential produces
a transient hyperpolarization of the membrane potential of the motor neuron
(See Figure 6.2). The time course of this hyperpolarization
looks very similar to that of an EPSP, but it is reversed in sign. The
synaptic potential in the motor neuron is called an inhibitory
postsynaptic potential (IPSP) because it tends to move the membrane potential
away from the threshold, thereby decreasing the probability of this neuron initiating
an action potential.
Ionic Mechanisms for IPSPs
The membrane potential of the flexor motor neuron is about -65 mV, so one might
predict that the IPSP would be due to an increase in the permeability or the conductance
of an ion whose equilibrium potential is more negative than -65 mV. One possibility
is potassium. Potassium does mediate some inhibitory synaptic potentials in the
central nervous system, but not at the particular synapse between a spinal interneuron
and spinal motor neuron. At this particular synapse, the IPSP is due to a selective
increase in chloride permeability. Note that the equilibrium potential for chloride
is about -70 mV. The transmitter released by the spinal interneuron binds to a
special class of ionotropic receptors which are normally closed, but open and
become selectively permeable to chloride ions as a result of the binding of the
transmitter. As a result of the increase in Cl- permeability, the membrane
potential moves from its resting value of -65 mV towards the Cl- equilibrium
potential. (Note that in principle, decreasing the resting conductance of Na+
could also produce an IPSP.)
Transmitter Substance of the Spinal Inhibitory Neuron
What about the transmitter substance that is released by the inhibitory interneuron
in the spinal cord? The transmitter substance is glycine,
an amino acid which is used frequently in the central nervous system as a transmitter
that produces inhibitory actions. It is not the most common, however. The most
common transmitter with inhibitory actions is gamma
amino butyric acid (GABA).
Metabotropic Synaptic
Responses
In addition to the responses mediated by ionotropic receptors, there is an entirely
separate class of synaptic potentials that have durations with orders of magnitude
greater than the durations of the classical EPSPs. These are so-called slow synaptic
potentials and they are mediated by metabotropic receptors. Slow synaptic potentials
are not observed at every postsynaptic neuron but they are certainly observed
at many. The figure below illustrates a postsynaptic neuron which receives two
inputs. An action potential in neuron 1 produces an excitatory postsynaptic potential
or EPSP in the postsynaptic cell whose duration is about 20 msec. Neuron 2 can
also produce a postsynaptic potential but its duration is more than three orders
of magnitude longer than that of the conventional type of synaptic potential.
The mechanism of these slow synaptic responses involves changes in metabolism
of the cell.
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Figure 6.5
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One mechanism for a slow synaptic potential is shown in the
illustration at left (Figure 6.5) and in Figure
11.11. In contrast to the ionotropic receptor for which the receptors
are actually part of the channel complex, the channels that produce the
slow synaptic potentials are not directly coupled to the transmitter receptors.
Rather, the receptors are separate from the channel. These receptors are
known as metabotropic because they involve changes in the metabolism of
the cell and, in general, changes in activation of specific second messenger
systems. The figure at left illustrates an example of one type of response
that involves the cyclic AMP cascade. Slow PSPs are in some cases mediated
by cyclic AMP but they are also mediated by other protein kinases. For the
response in Figure 6.5, the transmitter activates G proteins that lead to
the increased synthesis of cyclic AMP. Cyclic AMP then leads to the activation
of cyclic AMP-dependent kinase (PKA), which phosphorylates a channel protein
or a component of the channel and then produces a conformational change
in the channel and a change in its ionic permeability. In contrast to a
direct conformational change produced by the binding of a transmitter to
the receptor channel complex (seen in responses mediated by ionotropic receptors),
the conformational change is produced by phosphorylation. The particular
channel is one that is selectively permeable to K+ and is normally
open. As a result of the channel phosphorylation by PKA, the channel closes
and becomes less permeable to K+. Since the normal resting potential
is due to a balance of Na+ and K+, decreasing the
K+ conductance favors the effects of the Na+ conductance
and a depolarization is produced. |
It is interesting to point out that the activation of metabotropic receptors
can produce effects which are much longer than several hundred seconds. For
example, protein kinase A can diffuse in the nucleus where it can phosphorylate
proteins (i.e., transcription factors) that regulate gene expression.
Neurotoxins
The discovery of certain toxins has greatly facilitated the analysis of
voltage and chemically gated channels as well as the process of synaptic
transmission. The following table illustrates some that have been particularly
useful.
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SOME
IMPORTANT NEUROTOXINS
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| tetrodotoxin (TTX): |
Fish toxin that blocks the pore of voltage-dependent Na+
channels. |
| µ-conotoxin (µ-CTX): |
Fish-hunting cone snail toxin with properties similar to
TTX. |
| saxitoxin (STX): |
Toxin from marine dinoflagellates with properties similar
to TTX. STX is also known as paralytic shellfish poison. |
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| w-conotoxin (w-CTX): |
Fish-hunting cone snail toxin that blocks certain types
of voltage-dependent Ca2+ channels. |
| funnel web spider toxin (w-Aga): |
Toxin from funnel web spider which blocks certain types
of voltage-dependent Ca2+ channels. |
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| apamin: |
Bee venom toxin that blocks certain types of Ca2+-activated
K+ channels. |
| charybdotoxin (ChTX): |
Scorpion venom toxin that blocks pore of some Ca2+-activated
K+ channels and voltage-dependent K+ channels. |
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| curare (d-tubocuraine): |
Plant toxin that is a competitive inhibitor of nicotinic
ACh receptors. |
| a-bungarotoxin: |
Snake toxin that is competitive and highly irreversible
inhibitor of nicotinic ACh receptors. |
| picrotoxin: |
GABAA receptor blocker isolated from the
seed of Anamirta cocculus. |
| strychnine: |
Glycine receptor blocker isolated from the seed of the
East Indian tree Strychnos nux-vomica. |
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| tetanus toxin: |
Clostridial neurotoxin with zinc-dependent protease activity;
Cleaves synaptic vesicle proteins in the CNS and thereby blocks release
of neurotransmitters. |
| botulinum toxin: |
Clostridial neurotoxin with zinc-dependent protease activity;
Cleaves synaptic vesicle proteins at the neuromuscular junction and thereby
blocks release of ACh. |
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Contact the author(s) at: nba_course@uth.tmc.edu
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The University of Texas Health Science Center at Houston
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