The probability of transmitter release at a mammalian central synapse

Abstract

WHEN an action potential reaches a synaptic terminal, fusion of a transmitter-containing vesicle with the presynaptic membrane occurs with a probability (p_r) of less than one¹. Despite the fundamental importance of this parameter, p_r has not been directly measured in the central nervous system. Here we describe a novel approach to determine p_r monitoring the decrement of NMDA (N-methyl-D-aspartate)-receptor mediated synaptic currents in the presence of the use-dependent channel blocker MK-801 (ref. 2). On a single postsynaptic CA1 hippocampal slice neuron, two classes of synapses with a sixfold difference in p_r are resolved. Synapses with low p_r contribute to over half of transmission and are more sensitive to drugs enhancing transmitter release. Switching between these two classes of synapses provides the potential for large changes in synaptic efficacy and could underlie forms of activity-dependent plasticity.