A Simple Depletion Model of the Readily Releasable Pool of Synaptic Vesicles Cannot Account for Paired-Pulse Depression

Molecular Neurobiology Laboratory, Salk Institute, La Jolla, California; and Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, Washington Submitted 24 May 2006; accepted in final form 25 October 2006 Paired-pulse depression (PPD) is a form of short-term plasticity that plays a central role in processing of synaptic activity and is manifest as a decrease in the size of the response to the second of two closely timed stimuli. Despite mounting evidence to the contrary, PPD is still commonly thought to reflect depletion of the pool of synaptic vesicles available for release in response to the second stimulus. Here it is shown that PPD cannot be accounted for by depletion at excitatory synapses made by hippocampal neurons because PPD is unaffected by changes in the fraction of the readily releasable pool (RRP) released by the first of a pair of pulses. Address for reprint requests and other correspondence: J. M. Sullivan, Dept. of Physiology and Biophysics, Univ. of Washington School of Medicine, Box 357290, Seattle, WA 98195 (E-mail: jmsull{at}u.washington.edu )