Posttetanic potentiation (PTP) is similar to PPF; however, in this case the responses are compared before and after stimulation of the presynaptic neuron tetanically (tens to hundreds of stimuli at a high frequency). Such a tetanic stimulus train causes an increase in synaptic efficacy (see
Fig. 6.9C ). PTP, like PPF, is an enhancement of the postsynaptic response, but it lasts longer: tens of seconds to several minutes after the cessation of tetanic stimulation.
Numerous experiments have shown that PPF and PTP are the result of changes in the presynaptic terminal and do not generally involve a change in the sensitivity of the postsynaptic cell to transmitter. Rather, the repeated stimulation leads to an increased number of quanta of transmitter being released. This increase is thought to be due to residual amounts of Ca++ that remain in the presynaptic terminal after each stimulus and help potentiate subsequent release of transmitter. However, the exact mechanism or mechanisms by which this residual Ca++ enhances release is not yet clear. The residual Ca++ does not, however, appear to act simply by binding to the same sites as the Ca++ that enters at the active zone and directly triggers vesicle fusion in response to the action potential.
Use of a synapse can also lead to a short-term depression in its efficacy. Most commonly, the postsynaptic cell at such a fatigued or depressed synapse responds normally to transmitter applied from a micropipette; hence, as was the case for PPF and PTP, the change is presynaptic. In general, the depression is thought to reflect depletion of the number of releasable presynaptic vesicles. Thus, short-term depression of synaptic transmission is most often and most easily seen at synapses in which the probability of release after a single stimulus is high and under conditions that favor release (i.e., high [Ca++]). A postsynaptically related cause of synaptic depression can be desensitization of the receptors in the postsynaptic membrane.
Both potentiation and depressive processes can occur at the same synapse. So in general, the type of modulation observed will depend on which process dominates. This in turn can reflect stimulus parameters, local ionic conditions, and the properties of the synapse. In particular, synapses have different baseline probabilities for releasing vesicles. Synapses with a high release probability will be more likely to show poststimulus depression, whereas those with low release probability are less likely to deplete their vesicle store and thus can be facilitated more easily. Sometimes mixed responses can occur. For example, during a tetanic stimulus train a synapse may show a depressed response, but after the train the synapse can show posttetanic facilitation once the vesicles are recycled.
Just as the postsynaptic membrane contains receptors for neurotransmitters, so does the presynaptic membrane. When these presynaptic receptors bind neurotransmitter, they cause events that can modulate subsequent release of transmitter by the terminal. There are several sources of transmitter that bind to presynaptic receptors: it can be the transmitter released by the terminal itself (i.e., self-modulation, in which case the receptors are referred to as autoreceptors), it can be released by another presynaptic terminal that synapses onto the terminal (a serial synapse), or it can be a nonsynaptically acting neurotransmitter (see the section
Presynaptic receptors can be either ionotropic or metabotropic. In the latter case, recall that their action will be relatively slow in onset and long in duration and the effect will depend on the specific second messenger cascades that are activated. Such cascades can ultimately regulate presynaptic voltage-gated Ca++ and K+ channels and other presynaptic proteins and thereby alter the probability of vesicle release.