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Abstract

Background: The activity in neuronal networks with excitatory and inhibitory cells depend strongly on the balance between these two components. The balance of excitation and inhibition (E/I) is thought to crucially affect dynamics at the network level. How ever, an experimental platform that can investigate directly networks with differing E/I ratios is missing. We used sorting by a fluorescent activated cell sorter (FACS) on dissociated hippocampal cultures to control the E/I ratio to modify their network a ctivity. Results: Marked hippocampal neurons are sorted using FACS and seeded with changing E/I ratios to compose neuronal networks with particular inhibitory percent. We observed network bursts over long periods, and recorded burst amplitude, duration and inter burst interval (IBI) as a function of inhibitory percent. Remarkably, IBI values follow a U - shaped trend and remain constant in most E/I ratios, except in the extreme cases which are characterized by high IBI values. We used pharmacological agents t o monitor the network sensitivity to blocking of either inhibition or excitation. As expected, 0% inhibitory cultures are only slightly sensitive to the addition of an inhibitory blocker. While other cultures exhibit higher IBI values with higher amounts o f the blocker. A theoretical network model that is based on a balance between inhibition and excitation at the single cell level provides a striking and convincing comparison to the experimental results and clarifies the bursting dynamics in our cultures. Conclusions: Our experimental method enables the characterization of unique neuronal cultures, in which the relation between excitation and inhibition is controlled. E/I ratios were found to influence network activity, particularly the bursting features o f the culture and the network dynamics. Matching the experimental data to a theoretical model reveals the adaptive nature of neuronal networks and allows us to investigate the meaning of balance.