Network bursting dynamics in excitatory cortical neuron cultures results from the combination of different adaptive mechanism

Abstract

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