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 pre-synaptic 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 pre-synaptic 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.
Volman
Vladislav
V
School of Physics and Astronomy, Raymond & Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University, Tel-Aviv, Israel. volman@salk.edu
Gerkin
Richard C
RC
Lau
Pak-Ming
PM
Ben-Jacob
Eshel
E
Bi
Guo-Qiang
GQ
D000818:Animals; D001703:Biophysics / Q000379:methods*; D002118:Calcium / Q000378:metabolism*; D004594:Electrophysiology; D005071:Evoked Potentials; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D009415:Nerve Net; D009474:Neurons / Q000378:metabolism; D009991:Oscillometry; D013324:Strontium / Q000737:chemistry; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission
D002118:Calcium; D013324:Strontium