Evidence for an ephaptic feedback in cortical synapses: postsynaptic hyperpolarization alters the number of response...

The amplitude of excitatory postsynaptic potentials and currents increases with membrane potential hyperpolarization. This has been attributed to an increase in the driving force when the membrane potential deviates from the equilibrium potential of the respective ions. Here we report that in a subset of neocortical and hippocampal synapses, postsynaptic hyperpolarization affects traditional measures of transmitter release: the number of failures, coefficient of variation of response amplitudes, and quantal content, suggesting increased presynaptic release. The result is compatible with the hypothesis of Byzov on the existence of electrical (or "ephaptic") linking in purely chemical synapses. The linking, although negligible at neuromuscular junctions, could be functionally significant in influencing transmitter release at synapses with high resistance along the synaptic cleft. Our findings necessitate reconsideration of classical amplitude-voltage relations for such synapses. Thus, synaptic strength may be enhanced by hyperpolarization of the postsynaptic membrane potential. The positive ephaptic feedback could account for "all-or-none" excitatory postsynaptic potentials at some cortical synapses, large evoked and spontaneous multiquantal events and a high efficacy of large "perforated" synapses whose number increases following behavioural learning or the induction of long-term potentiation.