Presynaptic hyperpolarization induces a fast analogue modulation of spike-evoked transmission mediated by axonal sodium channels.

Sylvain Rama,Laure Fronzaroli-Molinieres,Edmond Carlier,Vincenzo Marra,Andrzej Bialowas,Norbert Ankri,Dominique Debanne,Mickaël Zbili

doi:10.1038/ncomms10163

Abstract

In the mammalian brain, synaptic transmission usually depends on presynaptic action potentials (APs) in an all-or-none (or digital) manner. Recent studies suggest, however, that subthreshold depolarization in the presynaptic cell facilitates spike-evoked transmission, thus creating an analogue modulation of a digital process (or analogue–digital (AD) modulation). At most synapses, this process is slow and not ideally suited for the fast dynamics of neural networks. We show here that transmission at CA3–CA3 and L5–L5 synapses can be enhanced by brief presynaptic hyperpolarization such as an inhibitory postsynaptic potential (IPSP). Using dual soma–axon patch recordings and live imaging, we find that this hyperpolarization-induced AD facilitation (h-ADF) is due to the recovery from inactivation of Nav channels controlling AP amplitude in the axon. Incorporated in a network model, h-ADF promotes both pyramidal cell synchrony and gamma oscillations. In conclusion, cortical excitatory synapses in local circuits display hyperpolarization-induced facilitation of spike-evoked synaptic transmission that promotes network synchrony.

Highlights

In the mammalian brain, synaptic transmission usually depends on presynaptic action potentials (APs) in an all-or-none manner
Pairs of monosynaptically connected CA3 neurons were recorded in organotypic cultures of the rat hippocampus after 8–10 days in vitro (DIV)[21]
The hyperpolarization-induced AD facilitation (h-ADF) was comparable when the presynaptic hyperpolarization amounted to À 84 or À 102 mV, suggesting that a presynaptic hyperpolarization of B10 mV is sufficient to obtain saturating h-ADF. h-ADF was associated with a reduced paired-pulse ratio (PPR, from 99±7 to 88±5%, n 1⁄4 12; Wilcoxon test Po0.05; Supplementary Fig. 1), indicating that it results from a presynaptic increase in glutamate release

Summary

Introduction

Synaptic transmission usually depends on presynaptic action potentials (APs) in an all-or-none (or digital) manner. That subthreshold depolarization in the presynaptic cell facilitates spike-evoked transmission, creating an analogue modulation of a digital process (or analogue–digital (AD) modulation) At most synapses, this process is slow and not ideally suited for the fast dynamics of neural networks. Neuronal information in the mammalian brain is generally transmitted through spike-evoked packets of neurotransmitter in a digital mode of signalling It has been recently shown, that subthreshold analogue activity in the presynaptic element might modulate this digital signalling, leading to the emergence of the concept of a hybrid analogue–digital (AD) facilitation of synaptic transmission. We show here that fast physiological hyperpolarization before the presynaptic action potential (AP) facilitates synaptic transmission in hippocampal and neocortical synaptic circuits This hyperpolarization-induced AD facilitation (h-ADF) is due to the recovery of Nav channels from inactivation, enhancing the spike amplitude in the axon. Interneurons paradoxically enhance excitatory transmission between pyramidal neurons and subsequently structure network dynamics

Methods

Results

Conclusion