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Excitation / Inhibition balance in living neuronal networks
{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\textpercent 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.}
@misc{item_3166391, title = {{Excitation / Inhibition balance in living neuronal networks}}, booktitle = {{28th Annual Meeting of the Israel Society for Neuroscience (ISFN 2019)}}, 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\textpercent 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.}}, pages = {148}, year = {2019}, slug = {item_3166391}, author = {Sukenik, N and Vinogradov, O and Levina, A and Moses, E} }