GABAergic interneurones can effectively synchronize the activity of principal cells giving rise to distinct oscillatory patterns. A particular rhythm, hippocampal theta oscillations (6-10Hz), links two ways of coding by which pyramidal cells in the hippocampus represent space, namely rate and phase coding. Thus, the theta cycle provides a clock against which the increased firing rate of pyramidal cells in the hippocampus and entorhinal cortex is measured. Furthermore, hippocampal theta is believed to constitute a link to episodic memory. Recent evidence from our lab indicates that recruitment of GABAergic interneurones critically affects certain aspects of hippocampus-dependent spatial memory in mice. We have established genetic tools that allow us to manipulate GABAergic interneurones in a cell type and region-specific manner. In combination with in vivo electrophysiology in the hippocampus/entorhinal cortex and behavioural studies, we will investigate how GABAergic interneurones regulate the activity in neuronal networks and contribute to behaviour. Specifically, we will address the following questions: 1) How does reduced recruitment of GABAergic interneurones affect network activity (theta oscillations)? 2) How does altered activity of GABAergic interneurones affect spatial representation (activity of place cells in the hippocampus and grid cells in the entorhinal cortex)? 3) How does modified activity in the hippocampus affect activity in the entorhinal cortex (and vice versa)? 4) How does modified network activity and spatial representation translate into spatial memory? The interdisciplinary approach will enable us to provide better insight into how cellular activity of GABAergic interneurones relates to network activity and ultimately to behaviour.
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