Genetic tools and imaging technology for mapping cholinergic engrams of anxiety

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 DESCRIPTION (provided by applicant): This application will develop new genetic tools and advance current procedures for precise and rapid mapping of behavior specific memory engrams. The proposed studies also will provide unique insight into the role of cholinergic signaling in the integrated networks that underlie anxiety behaviors. Modulatory transmitters that fine tune circuit activity are essential, albeit somewhat cryptic, components of neural coding. Perhaps the least understood- and yet most broadly distributed- neuromodulator in the CNS is acetylcholine (ACh). We propose to advance two aspects of genetic activity-mapping to track the extent to which cholinergic signaling is engaged by recall of anxiety-provoking experience in the mouse. Basal forebrain cholinergic neurons that display suprathreshold activation during recall of anxiety-induced behaviors are defined as enrolled in the memory engram (Eng+). Eng+ neurons will be mapped by genetically tagging activated cholinergic neurons and their projections from the basal forebrain to cingulate and prefrontal cortices as well as to hippocampal and amygdala regions that are implicated in anxiety related behavior.