Evidence for an ephaptic feedback in cortical synapses: Postsynaptic hyperpolarization alters the number of response failures and quantal content

The amplitude of excitatory postsynaptic potentials and currents increases with membrane potential hyperpolarization, This has been attributed to an i ncrease in the driving force when the membrane potential deviates from the equilibrium potential of the respective ions.(17) Here we report that in a subset of neocortical and hippocampal synapses, postsynaptic hyperpolarizat ion affects traditional measures of transmitter release: the number of fail ures, coefficient of variation of response amplitudes, and quantal content, suggesting increased presynaptic release. The result is compatible with th e hypothesis of Byzov(4,5) On the existence of electrical (or "ephaptic"(15 )) linking in purely chemical synapses. The linking, although negligible at neuromuscular junctions,(17,27) could be functionally significant in influ encing transmitter release at synapses with high resistance along the synap tic cleft.(5,33) Our findings necessitate reconsideration of classical ampl itude-voltage relations for such synapses. Thus, synaptic strength may be e nhanced by hyperpolarization of the postsynaptic membrane potential. The po sitive ephaptic feedback could account for "all-or-none" excitatory postsyn aptic potentials at some cortical synapses,(25,30) large evoked(7) and spon taneous(18) multiquantal events and a high efficacy of large "perforated" s ynapses whose number increases following behavioural learning(6) or the ind uction of long-term potentiation,(9,12). (C) 1999 IBRO. Published by Elsevi er Science Ltd.