ATYPICAL DELAYED CALCIUM-DEPENDENT PAIRED-PULSE DEPRESSION AT IDENTIFIED SYNAPSES

Plasticity at chemical synapses depends on the interplay between the stimulation pattern, the dynamics of presynaptic calcium concentration and the use and replenishment of the vesicle pool. Synaptic facilitation is caused by an increased probability of release (PR) due to presynaptic calcium accumulation, while synaptic depression is attributed to depletion of the releasable vesicle pool. These phenomena may coexist, with their relative contribution depending mostly on the initial PR: low PR allows synaptic facilitation, while high PR leads to synaptic depression. Here we show an unusual form of paired-pulse delayed depression at synapses between P and AP neurons of the leech. Two presynaptic impulses with short (<700ms) inter-stimulus intervals produced facilitation, which extinguished exponentially, consistent with the residual calcium hypothesis, and showing that a single impulse does not deplete the vesicle pool. However, long (>700ms) inter-stimulus intervals produced delayed depression, that increased with the interval up to 1000ms, abruptly deviating from the facilitation decrease curve, not with the continuous transition expected from a gradual decrease in RP and a slow recovery of the vesicle pool. Strong facilitation could be elicited after delayed depression, even when depression increased by increasing previous release. Delayed depression was calcium-dependent, as it was reduced by pre-incubation with EGTA-AM. Our data cannot be explained by classical models of plasticity solely considering vesicular depletion-replenishment and calcium-dependent changes in RP but are fully captured by a new model that includes a slow calcium-dependent mechanism removing vesicles from the readily releasable pool with a delay after each presynaptic impulse.