4.6 Article

Network Bursting Dynamics in Excitatory Cortical Neuron Cultures Results from the Combination of Different Adaptive Mechanism

Journal

PLOS ONE
Volume 8, Issue 10, Pages -

Publisher

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0075824

Keywords

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Funding

  1. European Union [269459]
  2. ERC [295129]
  3. Spanish Research Project [SAF2010-16085]
  4. CONSOLIDER-INGENIO Program [CSD2007-00012]
  5. European Research Council (ERC) [295129] Funding Source: European Research Council (ERC)
  6. ICREA Funding Source: Custom

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In the brain, synchronization among cells of an assembly is a common phenomenon, and thought to be functionally relevant. Here we used an in vitro experimental model of cell assemblies, cortical cultures, combined with numerical simulations of a spiking neural network (SNN) to investigate how and why spontaneous synchronization occurs. In order to deal with excitation only, we pharmacologically blocked GABA(A)ergic transmission using bicuculline. Synchronous events in cortical cultures tend to involve almost every cell and to display relatively constant durations. We have thus named these network spikes'' (NS). The inter-NS-intervals (INSIs) proved to be a more interesting phenomenon. In most cortical cultures NSs typically come in series or bursts (bursts of NSs'', BNS), with short (similar to 1 s) INSIs and separated by long silent intervals (tens of s), which leads to bimodal INSI distributions. This suggests that a facilitating mechanism is at work, presumably short-term synaptic facilitation, as well as two fatigue mechanisms: one with a short timescale, presumably short-term synaptic depression, and another one with a longer timescale, presumably cellular adaptation. We thus incorporated these three mechanisms into the SNN, which, indeed, produced realistic BNSs. Next, we systematically varied the recurrent excitation for various adaptation timescales. Strong excitability led to frequent, quasi-periodic BNSs (CV similar to 0), and weak excitability led to rare BNSs, approaching a Poisson process (CV similar to 1). Experimental cultures appear to operate within an intermediate weakly-synchronized regime (CV similar to 0.5), with an adaptation timescale in the 2-8 s range, and well described by a Poisson-with-refractory-period model. Taken together, our results demonstrate that the INSI statistics are indeed informative: they allowed us to infer the mechanisms at work, and many parameters that we cannot access experimentally.

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