External and internal controllers of hippocampal SPW-R initiation

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Sharp wave ripples (SPW-Rs) are self-organized, synchronized population events in which hippocampal circuit excitability is markedly and transiently enhanced. The temporal distribution of SPW-Rs is highly irregular and strongly influenced by behavioral and brain states, indicating the existence of control mechanisms for the initiation of these population events and the memory replay which they support. There is accumulating evidence that suggests that SPW-Rs occurrence is controlled by both extra-hippocampal and intra-hippocampal influences. However, the precise distal and local circuit mechanisms by which these extra- and intra-hippocampal influences control SPW-R initiation are unknown. In Project 1, we will perform a comprehensive set of studies which will provide new information on the precise temporal relationship (through observational experiments using integrated high-resolution methods) and perturbational influence (using optogenetic interventions) of key suspected extra- and intra-hippocampal controllers of SPW-R initiation.