Projects

A tight balance of excitation and inhibition is fundamental to keep the cortex in a functional and healthy operating regime. Intriguingly, the network configuration of the cortex, i.e. its connectome, is highly dynamic even under basal conditions. It is unclear how the balance of excitation and inhibition is established and maintained in light of a dynamic connectome. Here we propose and seek to test the ‘self-organized excitatory/inhibitory-balance’-hypothesis which states that the turnover of excitatory and inhibitory synapses takes place in concert to keep their overall contribution balanced and this balance emerges spontaneously as a dynamical equilibrium through the interaction of different plasticity mechanisms. To test this hypothesis we will i) measure the cortical connectome with an unprecedented scope using in vivo time lapse imaging of both excitatory and inhibitory synapses ii) develop automated analysis techniques to quantify in a rigorous and objective way simultaneous changes occurring in large groups of excitatory and inhibitory synapses and iii) use these data to build and constrain a computational network model aiming to describe these changes by assuming a limited set of neural plasticity rules. We then use this model to predict the consequences of enhancing inhibition on subsequent changes in excitatory and inhibitory synapses, and test its prediction in vivo by using Diazepam, a well-known enhancer of GABAergic transmission. The proposed research will shed light on the dynamic nature of the connectome and the mechanisms giving rise to the exquisite balance between excitation and inhibition in the brain. Our study has translational implications as disturbances in the balance of excitation and inhibition have been shown to contribute to forms of psychiatric diseases as well as epilepsy.

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