Calcium and synaptic dynamics underlying reverberatory activity in neuronal networks

TL;DR

This study presents a biophysical model explaining how residual presynaptic calcium and asynchronous transmitter release sustain reverberatory activity in neuronal networks, shedding light on cellular mechanisms of persistent neural activity.

Contribution

The paper introduces a novel biophysical model linking residual calcium dynamics and asynchronous release to reverberatory activity in cultured hippocampal networks.

Findings

Reverberatory activity depends on residual presynaptic calcium.

Asynchronous transmitter release sustains network reverberations.

Fast and slow synaptic depression control initiation and termination of reverberations.

Abstract

Persistent activity is postulated to drive neural network plasticity and learning. To investigate its underlying cellular mechanisms, we developed a biophysically tractable model that explains the emergence, sustenance, and eventual termination of short-term persistent activity. Using the model, we reproduced the features of reverberating activity that were observed in small (50-100 cells) networks of cultured hippocampal neurons, such as the appearance of polysynaptic current clusters, the typical inter-cluster intervals, the typical duration of reverberation, and the response to changes in extra-cellular ionic composition. The model relies on action potential-triggered residual presynaptic calcium, which we suggest plays an important role in sustaining reverberations. We show that reverberatory activity is maintained by enhanced asynchronous transmitter release from pre-synaptic terminals, which in itself depends on the dynamics of residual presynaptic calcium. Hence, asynchronous release, rather than being a "synaptic noise", can play an important role in network dynamics. Additionally, we found that a fast timescale synaptic depression is responsible for oscillatory network activation during reverberations, whereas the onset of a slow timescale depression leads to the termination of reverberation. The simplicity of our model enabled a number of predictions that were confirmed by additional analyses of experimental manipulations.