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C04 Global and local inhibition in the normal and epileptic dentate gyrus

Central neurons receive thousands of excitatory synapses onto synaptic spines emanating from their dendrites. How neurons convert spatiotemporal patterns of synaptic inputs to an action potential output that allows synaptic signalling to downstream neuronal ensembles is fundamental to brain function. The input-output conversion of central neurons is powerfully controlled by inhibitory synapses that derive from different types of interneurons, activated by feed-back and feed-forward circuits. The efficacy of inhibitory systems in controlling synaptic integration and action potential output depends on the relative topology, timing and biophysical properties of inhibitory and excitatory synapses. Using novel light-based photomanipulation techniques, we propose to examine the effects of different types of inhibition on signal integration in hippocampal dentate granule cells. To achieve these goals, we will use a combination of multiphoton glutamate uncaging/imaging techniques, optogenetics, in-vitro and in-vivo electrophysiology as well as behavioural experiments. We will also extend these studies to experimental models of epilepsy, as well as human tissue resected from epilepsy patients during epilepsy surgery, in which the dentate gyrus is frequently well-preserved. We expect that this study will yield new insights into local and global excitatory-inhibitory interactions within the dendritic tree of neurons, as well as into the importance of inhibitory systems in the dentate gyrus for behaviour.