Short-term forms of presynaptic plasticity

Abstract

Synapses exhibit several forms of short-term plasticity that play a multitude of computational roles. Short-term depression suppresses neurotransmitter release for hundreds of milliseconds to tens of seconds; facilitation and post-tetanic potentiation lead to synaptic enhancement lasting hundreds of milliseconds to minutes. Recent advances have provided insight into the mechanisms underlying these forms of plasticity. Vesicle depletion, as well as inactivation of both release sites and calcium channels, contribute to synaptic depression. Mechanisms of short-term enhancement include calcium channel facilitation, local depletion of calcium buffers, increases in the probability of release downstream of calcium influx, altered vesicle pool properties, and increases in quantal size. Moreover, there is a growing appreciation of the heterogeneity of vesicles and release sites and how they can contribute to use-dependent plasticity.

Figure 1

Presynaptic mechanisms of use-dependent short-term plasticity. Schematic diagrams illustrate proposed mechanisms for depression (a), facilitation (b), and post-tetanic potentiation (PTP) and augmentation (c). RRP: readily releasable pool of vesicles; Ca_res: residual calcium.

Figure 2

Two common approaches of assessing vesicle pools relevant to understanding the mechanisms of short-term plasticity. One approach to assessing the properties of vesicles is to stimulate synapses at high frequencies under conditions where desensitization and saturation of postsynaptic receptors are blocked (a, top). (a, bottom) The amplitudes of the synaptic currents evoked by each stimulus are then measured, and a graph is made of the cumulative excitatory postsynaptic current (EPSC). When these values are divided by the amplitude of miniature EPSCs (mEPSCs) they represent the cumulative number of vesicles. The readily releasable pool liberated by the stimulus train (RRP_train) is then determined by fitting over a linear region of this curve and extrapolating back to zero. (b) Another approach is to provide a prolonged voltage step that opens presynaptic calcium channels for a long time. The resulting postsynaptic currents then provide a measure of the readily releasable pool (again using the mEPSC size to convert from current to number of vesicles). The total number of vesicles liberated is the readily releasable pool (RRP), which consists of a fast component (RRP_fast) and a slow component (RRP_slow). As discussed in the text, synaptic plasticity can affect RRP_train without influencing RRP. Understanding RRP_train, RRP_fast, RRP_slow, and RRP has important implications for determining the mechanisms underlying short-term plasticity.