Calcium and synaptic dynamics underlying reverberatory activity in neuronal networks

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.

💡 Research Summary

Persistent, short‑lasting reverberatory activity has long been implicated in the formation of neural plasticity and memory, yet the cellular and synaptic mechanisms that generate, sustain, and eventually terminate such activity remain poorly defined. In this study the authors constructed a minimal yet biophysically grounded computational model that captures the essential dynamics of small (≈50–100 cells) cultured hippocampal networks, reproducing the hallmark features observed experimentally: discrete clusters of polysynaptic currents, a characteristic inter‑cluster interval of roughly half a second, overall reverberation durations of 5–15 seconds, and systematic modulation by extracellular ion composition.

The core of the model is the concept of residual presynaptic calcium (