The Role of Inhibitory Mechanisms on Governing the Hippocampal Temporal Code

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DESCRIPTION (provided by applicant): The hippocampus has a well established role in learning and memory (Scoville & Milner, 1957; Squire, 1992), and hippocampal damage is primarily responsible for the memory impairments resulting from a variety of neurological conditions such as Alzheimer's disease, epilepsy and stroke. In vivo electrophysiological studies of the hippocampus have revealed some salient activity patterns. Specifically, hippocampal cells in both rodents and humans fire in a spatially selective manner (O'Keefe and Dostrovsky, 1971; O'Keefe and Recce, 1993; Ekstrom et al., 2003, 2005). Both the firing-rate (rate code) and spike-timing (temporal code) contain information about the spatial environment. However, the cellular and circuit mechanisms that give rise to the hippocampal rate and temporal codes are still not well understood, and little is known about how inhibition shapes these hippocampal activity patterns. I will combine in vivo and in vitro experiments with computational modeling to investigate the inhibitory mechanisms governing the hippocampal temporal code. Using such an understanding, we can precisely pinpoint what properties of the circuit are crucial for hippocampal function. This can point us towards novel targets for treating clinical ailments resulting from hippocampal damage. Relevance: The human hippocampus is important for learning and memory but it is prone to damage: strokes, dementias (including Alzheimer's disease), epilepsies and hypoxia can all lead to hippocampal damage, and subsequent learning and memory difficulties. By understanding the neural code of the hippocampus we can precisely pinpoint which of its cells and circuits are crucial for learning and memory. This can point us towards novel targets for treating problems resulting from hippocampal damage.