Postsynaptic hyperpolarization increases the strength of AMPA-mediated synaptic transmission at large synapses between mossy fibers and CA3 pyramidalcells

In chemical synapses information flow is polarized. However, the postsynapt ic cells can affect transmitter release via retrograde chemical signaling. Here we explored the hypothesis that, in large synapses, having large synap tic cleft resistance, transmitter release can be enhanced by electrical (ep haptic) signaling due to depolarization of the presynaptic release site ind uced by the excitatory postsynaptic current itself. The hypothesis predicts that, in such synapses, postsynaptic hyperpolarization would increase resp onse amplitudes isupralinearly", i.e. stronger than predicted from the driv ing force shift. We found supralinear increases in the amplitude of minimal excitatory postsynaptic potential (EPSP) during hyperpolarization of CA3 p yramidal neurons. Failure rate, paired-pulse facilitation, coefficient of v ariation of the EPSP amplitude and EPSP quantal content were also modified. The effects were especially strong on mossy fiber EPSPs (MF-EPSPs) mediate d by the activation of large synapses and identified pharmacologically or b y their kinetics. The effects were weaker on commissural fiber EPSPs mediat ed by smaller and more remote synapses. Even spontaneous membrane potential fluctuations were associated with supralinear MF-EPSP increases and failur e rate reduction. The results suggest the existence of a novel mechanism fo r retrograde control of synaptic efficacy from postsynaptic membrane potent ial and are consistent with the ephaptic feedback hypothesis. (C) 2000 Else vier Science Ltd. All rights reserved.