Intrasynaptic ephaptic feedback in central synapses

Electrophysiological laboratory studies on rat visual cortex and hippocampus slices are reviewed. The aim was to confirm the existence of positive feedback in central synapses operating by an electrical (ephaptic) mechanism, as suggested by Byzov. Byzov's hypothesis holds that artificial hyperpolarization of the postsynaptic membrane potential should increase the amplitude of the excitatory postsynaptic current (EPSC) and potential (EPSP) in some central synapses not only by means of increases in the electromotive force (EMF). but also by means of increases in transmitter release from the presynaptic apparatus. Some experiments showed that hyperpolarization altered the parameters of presynaptic transmitter release, i.e., the quantity of "failed" responses N0, the coefficient of variation CV, and the quantum composition m of minimal EPSC and EPSP. The effect was particularly marked for EPSP in giant synapses formed by mossy fibers on neurons in field CA3. "Supralinear" functions were observed for these synapses in the relationship between EPSC amplitude and membrane potential in conditions of hyperpolarization of membrane potentials and in the relationship between presynaptic paired-stimulus facilitation and membrane potential. All of these "non-classical" effects disappeared when summed rather than minimal EPSC were evoked. The results are in agreement with computer experiments based on the Byzov model and are regarded as support for Byzov's hypothesis. Regardless of their explanation, the data obtained here demonstrate a new feedback mechanism for central synapses, which allows the postsynaptic neuron to control the efficiency of some synapses via changes in membrane potential. This mechanism can significantly increase the efficiency of large ("perforated") synapses and explains the increase in the number of this type of synapse after various experimental manipulations, such as those inducing long-term potentiation or forming conditioned reflexes.