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The spread of subthreshold somatic voltage fluctuations into the axon modulates spike-evoked synaptic transmission. In neocortical L5 pyramidal neurons, depolarization-induced facilitation of synaptic efficacy is thought to occur through the enlargement of presynaptic action potential (AP) driven by inactivation of axonal Kv1 potassium channels. We report here in hippocampal slice cultures that synaptic transmission at excitatory CA3-CA3 synapses also depends on the membrane potential of the presynaptic neuron (Vm-pre). In synaptically connected cell-pairs, presynaptic APs produced postsynaptic response recorded in voltage (EPSC) or current-clamp (EPSP) configuration. Synaptic transmission was tested when Vm-pre was held continuously at rest (-61 mV), hyperpolarized (-77 mV) or depolarized potential (-48 mV). The presynaptic voltage facilitation (PVF) of synaptic transmission was quantified by normalizing the postsynaptic responses obtained at -48 mV to those measured at -77 mV. In these conditions, PVF amounted to 135 ± 14% and was associated with a decrease in the paired-pulse ratio. We found that PVF was totally occluded by bath application of the Kv1 channel blocker DTX. Time constant of PVF was determined by evoking single presynaptic APs at increasing delays after the onset of a presynaptic depolarization. The measured time constant (2 s) was compatible with the time constant of the inactivation of D-type current carried by Kv1 channels. Using confocal laser scanning microscopy and Fluo-4 fluorescent calcium indicator, we measured calcium transients in axons of CA3 pyramidal neurons. Depolarization of the cell body from -65 to -50 mV enhanced spike-evoked axonal calcium transients by ~30%. Notably, this facilitation followed the time course of the PVF. We conclude that PVF is a short-term plasticity present at excitatory CA3-CA3 synapses resulting from the increase in spike-evoked calcium transients in the axon caused by voltage-inactivation of Kv1 channels.
Synaptic transmission in the brain generally depends on action potentials. However, subthreshold variation in presynaptic membrane potential also determines spike-evoked transmission. We show here that excitatory synaptic transmission at CA3–CA3 connections depends on the membrane potential of the presynaptic neuron. Connected CA3 pyramidal neurons were recorded and synaptic transmission was tested when the presynaptic neurone was held at −61 mV, −77 mV or −48 mV. The presynaptic voltage facilitation (PVF) of synaptic transmission quantified by normalizing the postsynaptic responses obtained at −48 mV to those measured at −77 mV amounted to 135 ± 14% (n=13). PVF was associated with a decrease in the paired-pulse ratio and was totally occluded by bath application of the Kv1 channel blocker dendrotoxin (DTX). Using confocal laser scanning microscopy, we measured calcium transients evoked by the propagated spike in axons (50–250 µm from the soma) of CA3 neurons loaded with Fluo-4. Depolarization of the cell body from −75 to −50 mV enhanced spike-evoked calcium transients by ~17%. We conclude that PVF is a short-term plasticity at excitatory CA3–CA3 synapses resulting from the increase in spike-evoked calcium transients in the axon caused by voltage-inactivation of Kv1 channels.
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