Differences in amplitude-voltage relations between minimal and composite mossy fibre responses of rat CA3 hippocampal neurons support the existence of intrasynaptic ephaptic feedback in large synapses

Computer simulations and electrophysiological experiments have been perform ed to test the hypothesis on the existence of an ephaptic interaction in pu rely chemical synapses. According to this hypothesis, the excitatory postsy naptic current would depolarize the presynaptic release site and further in crease transmitter release, thus creating an intrasynaptic positive feedbac k. For synapses with the ephaptic feedback, computer simulations predicted non-linear amplitude-voltage relations and voltage dependence of paired-pul se facilitation. The deviation from linearity depended on the strength of t he feedback determined by the value of the synaptic cleft resistance. The s imulations showed that, in the presence of the intrasynaptic feedback, recr uitment of imperfectly damped synapses and synapses with linear amplitude-v oltage relations tended to reduce the non-linearity and voltage dependence of paired-pulse facilitation. Therefore, the simulations predicted that the intrasynaptic feedback would particularly affect small excitatory postsyna ptic currents induced by activation of electrotonically close synapses with long synaptic clefts. In electrophysiological experiments performed on hip pocampal slices, the whole-cell configuration of the patch-clamp technique was used to record excitatory postsynaptic currents evoked in CA3 pyramidal cells by activation of large mossy fibre synapses. In accordance with the simulation results, minimal excitatory postsynaptic currents exhibited "sup ralinear" amplitude-voltage relations at hyperpolarized membrane potentials , decreases in the failure rate and voltage-dependent paired-pulse facilita tion. Composite excitatory postsynaptic currents evoked by activation of a large amount of presynaptic fibres typically bear linear amplitude-voltage relationships and voltage-independent paired-pulse facilitation. These data are consistent with the hypothesis on a strong ephaptic feedback in large mossy fibre synapses. The feedback would provide a mechanism wher eby signals from large synapses would be amplified. The ephaptic feedback w ould be more effective on synapses activated in isolation or together with electrotonically remote inputs. During synchronous activation of a large nu mber of neighbouring inputs, suppression of the positive intrasynaptic feed back would prevent abnormal boosting of potent signals. (C) 2000 IBRO. Publ ished by Elsevier Science Ltd. All rights reserved.