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Modules of coordinated activity in hippocampal subfields during associative memory formation

Lena Johanna Gschossmann1, Fabian Distler1, Heinz Beck1

1 University of Bonn

Animals rely on the capacity to associate temporally discontinuous events in order to learn essential relationships governing their environment. In rodents, the dorsal hippocampus is known to be necessary for this type of learning, but the underlying mechanisms are insufficiently understood. In this project, we therefore probed neural activity of the three major hippocampal subregions – dentate gyrus, CA3, CA1 – using multiphoton Ca2+ imaging in head-fixed mice while they learned the association between a neutral (tone) and an aversive (airpuff) stimulus, which were separated by a delay (trace) period. In all three subregions, very few neurons displayed significant responses to either of the stimuli. Moreover, we could not identify sequential activity patterns bridging the trace interval. However, a subset of stimulus-responsive neurons in the subfields CA3 and CA1 exhibited remarkably reliable responses after the tone or airpuff stimulation during conditioning sessions. Interestingly, groups of neurons with a similar stimulus-sensitivity also displayed highly correlated activity in the inter-trial-interval and this effect was more pronounced in CA3 compared to CA1. A subgroup of neurons responding to both tone and airpuff also displayed correlated activity with each other, but much less pronounced correlations with neurons responding to only tone or airpuff. These findings suggest the presence of modules consisting of relatively few neurons in CA3 and CA1 that reliably react to salient events and could act as anchors in the stream of ongoing neural activity. How these modules arise and if they are important for memory consolidation is the subject of future studies.