DENTATE GYRUS NEURAL CODE FOR PATTERN SEPARATION

The formation of accurate memories depends, in part, on the distinction between similar, but distinct, stimuli and situations, and this ability is impaired in several neuropsychiatric pathologies. The dentate gyrus (DG) of the hippocampus performs this computation, called pattern separation (PS). Although the DG is known to be necessary for discriminating between similar contexts, no prior study has characterized in vivo the underlying neural code. We injected Cre-dependent GCaMP7c into the dorsal DG (dDG) of dock10-Cre mice, restricting expression to mature granule cells, and imaged their activity during a behavioral PS task. After fear conditioning in context A, mice underwent daily exposures to context A (reinforced with a foot shock) and to a similar but different context B (safe) for 9 days. Mice successfully acquired conditioned fear responses to context A, initially generalizing them to context B, but learned over days to discriminate between contexts. We then compared dDG activity during fear acquisition, generalization and discrimination between contexts. We found that the global number of active cells was stable across PS days and trials, and average event rates were not significantly different per trial across days. However, when comparing freezing epochs specifically, we found that event rates change in the safe context B between peak generalization and behavioral discrimination, from being similar to event rates in context A, to becoming distinct. Here we have characterized how the dDG represents context at both the cell ensemble and activity levels. Future analyses will delve into abstract representations at the neural population level.