Weak electric current stimulation and optogenetics to investigate sleep-dependent memory consolidation and ensemble reactivation

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Investigations on the consolidation of sleep-associated hippocampus dependent memories have focussed on hippocampal reactivation and hippocampo-prefrontal interactions during non-rapid eye movement sleep. Recently, the role of thalamic matrix nuclei as a hub for bidirectional hippocampal-prefrontal interactions has become of interest. In the previous funding period we developed tools to interrogate prefrontal and hippocampal network oscillations using optogenetic and closed-loop weak electric current stimulation. Our results revealed that endogenous oscillations can be entrained by optogenetic stimulation. Moreover, induced changes in the rhythm dynamics affected exploratory behaviour and recapitulated correlations between spontaneous synchronization and behaviour indicating a causal functional connection. Studies of others and our preliminary findings suggest that the effects of weak electric current stimulation, which simulates subthreshold activity, are most sensitive to ongoing network oscillations reflecting behavioural and vigilance state-dependence. Memory consolidation during sleep is linked to the orchestration of cross-regional network oscillations, as the sleep slow oscillation. Here, using experimental and analytical tools to-be developed in the project we aim firstly to define a cross-regional pattern of activity predictive of memory acquisition and consolidation. Secondly, employing multi-regional closed-loop weak electrical and optogenetic stimulation protocols we aim to improve sleep-associated memory consolidation by manipulating its endogenous electrophysiological signatures. Thirdly, in this process we will develop novel tools for optogenetic and weak electric network interrogation.