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Zusammenfassung:
Network bursting is the most common type of spontaneous activity of neuronal cultures. Inhibition has been shown to modify the bursting activity, however, mechanistic understanding of the role of inhibition has not been established. In this study, we focus on explaining spontaneous and pharmacologically induced dynamics of hippocampal cultures with various numbers of inhibitory cells. We propose a model that closely matches statistics of culture’s activity and provides an interpretation for the effects of i nhibitory neurons on the global dynamics. We designed a network of randomly connected leaky integrate - and - fire neurons with adaptive synapses. Three scenarios are considered: fully excitatory network, networks with tentatively balanced excitation and inhib ition with a different number of inhibitory cells, and inhibition - dominated network with a few strongly connected excitatory neurons. Simulation of the network shows that the model can predict changes in inter - burst intervals (IBI) and the effects of pharm acological manipulations in cultures with various numbers of inhibitory neurons. Both the model and data show that the IBI stays constant for all but extreme percentages of inhibitory cells. At the same time, the variance of IBI grows with the relative num ber of inhibitory cells, and blockage of GABA receptors results in longer IBI only in cultures with inhibitory neurons. The model suggests that inhibition stops the burst before the adaptation completely silence the network. This, in turn, allows the next burst to start earlier, leading to the shorter IBI. In the fully excitatory network, however, the IBI are given by the adaptation alone. Finally, in the inhibition dominated network, the activity rarely propagates through the whole network. Thus, the model emphasizes the importance of adaptation for neuronal cultures and shows how tight balance between excitation and inhibition neurons can specifically adjust adaptation to generate various bursting dynamics.
