Calcium and synaptic dynamics underlying reverberatory activity in neuronal networks

Phys Biol. 2007 Jun 11;4(2):91-103. doi: 10.1088/1478-3975/4/2/003.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biophysics / methods*
  • Calcium / metabolism*
  • Electrophysiology
  • Evoked Potentials
  • Hippocampus / metabolism*
  • Humans
  • Models, Biological
  • Models, Statistical
  • Nerve Net
  • Neurons / metabolism
  • Oscillometry
  • Strontium / chemistry
  • Synapses / metabolism*
  • Synaptic Transmission


  • Calcium
  • Strontium