Kinetic Isolation of a Slowly Recovering Component of Short-Term Depression During Exhaustive Use at Excitatory Hippocampal Synapses

Abstract

This study examines the kinetics of the longest lasting form of short-term depression at excitatory hippocampal synapses. After initial depletion of the readily releasable pool (RRP), continued 20-Hz stimulation was found to be fast enough to maximally drive presynaptic neurotransmitter exocytosis; maximal is defined here as the rate needed to maintain the RRP in a nearly empty steady state. Induction of depression proceeded in two distinct phases. The first was caused by RRP depletion, whereas the second is shown to reflect the progressive reduction of the overall rate at which new vesicles are supplied to the RRP and is termed “supply-rate depression.” Supply-rate depression is identified further with the emergence, during heavy use, of a rate-limiting vesicle trafficking step that slows the timing of RRP replenishment by switching from a fast (τ ≅ 7 s) to a slow (τ ≅ 1 min) vesicle supply mechanism. Both mechanisms apparently follow first-order kinetics. After the induction of the maximum amount of depression, individual synapses were able to output only