Posttetanic potentiation (PTP) is similar to PPF. However, in PTP, the postsynaptic responses are compared before and after the presynaptic neuron is stimulated tetanically (with tens to hundreds of stimuli at a high frequency). This tetanic stimulus train causes an increase in synaptic efficacy. PTP, like PPF, enhances the postsynaptic response, but it lasts longer - from tens of seconds to several minutes after the tetanic stimulation stops.

Numerous experiments have demonstrated that both PPF and PTP are caused by changes in the presynaptic terminal and do not typically involve a change in the sensitivity of the postsynaptic cell to the transmitter. Instead, repeated stimulation leads to an increased release of transmitter quanta. This increase is believed to be due to residual amounts of Ca++ that remain in the presynaptic terminal after each stimulus, helping potentiate subsequent release of the transmitter. However, the exact mechanism by which this residual Ca++ enhances release is not yet fully understood. It is known that the residual Ca++ does not simply bind to the same sites as the Ca++ that enters at the active zone and triggers vesicle fusion in response to the action potential.

Using a synapse can also result in a short-term depression in its efficacy. Typically, the postsynaptic cell at a fatigued or depressed synapse responds normally to transmitter applied from a micropipette, indicating that the change is presynaptic. The depression is thought to be caused by a depletion of the number of releasable presynaptic vesicles. Therefore, short-term depression of synaptic transmission is commonly observed at synapses with a high probability of release after a single stimulus and under conditions favoring release (i.e., high [Ca++]). Additionally, synaptic depression can be caused by desensitization of the receptors in the postsynaptic membrane.

Both potentiation and depressive processes can occur at the same synapse, and the type of modulation observed depends on which process dominates. This, in turn, can be influenced by stimulus parameters, local ionic conditions, and the properties of the synapse. Synapses with a high release probability are more likely to show poststimulus depression, while synapses with low release probability are less likely to deplete their vesicle store and can be facilitated more easily. Mixed responses can sometimes occur, for example, a synapse may exhibit a depressed response during a tetanic stimulus train but show posttetanic facilitation once the vesicles are recycled.

Similar to the postsynaptic membrane, the presynaptic membrane also contains receptors for neurotransmitters. When these presynaptic receptors bind neurotransmitter, they can modulate subsequent release of transmitter by the terminal. There are several sources of neurotransmitter that bind to presynaptic receptors: it can be the transmitter released by the terminal itself (self-modulation), released by another presynaptic terminal that synapses onto the terminal (serial synapse), or a nonsynaptically acting neurotransmitter.

Presynaptic receptors can be either ionotropic or metabotropic. In the case of metabotropic receptors, their action is relatively slow in onset and long in duration. The effect of these receptors depends on the specific second messenger cascades that are activated. These cascades can ultimately regulate presynaptic voltage-gated Ca++ and K+ channels, as well as other presynaptic proteins, thereby altering the probability of vesicle release.
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.