Connectivity, excitability and activity patterns in neuronal networks

Extremely synchronized firing patterns such as those observed in brain diseases like epilepsy may result from excessive network excitability. Although network excitability is closely related to (excitatory) connectivity, a direct measure for network excitability remains unavailable. Several methods currently exist for estimating network connectivity, most of which are related to cross-correlation. An example is the conditional firing probability (CFP) analysis which calculates the pairwise probability (CFPi,j) that electrode j records an action potential at time t = τ, given that electrode i recorded a spike at t = 0. However, electrode i often records multiple spikes within the analysis interval, and CFP values are biased by the on-going dynamic state of the network. Here we show that in a linear approximation this bias may be removed by deconvoluting CFPi,j with the autocorrelation of i (i.e. CFPi,i), to obtain the single pulse response (SPRi,j)-the average response at electrode j to a single spike at electrode i. Thus, in a linear system SPRs would be independent of the dynamic network state. Nonlinear components of synaptic transmission, such as facilitation and short term depression, will however still affect SPRs. Therefore SPRs provide a clean measure of network excitability. We used carbachol and ghrelin to moderately activate cultured cortical networks to affect their dynamic state. Both neuromodulators transformed the bursting firing patterns of the isolated networks into more dispersed firing. We show that the influence of the dynamic state on SPRs is much smaller than the effect on CFPs, but not zero. The remaining difference reflects the alteration in network excitability. We conclude that SPRs are less contaminated by the dynamic network state and that mild excitation may decrease network excitability, possibly through short term synaptic depression.