CA3 PYRAMIDAL CELLS ARE ORGANIZED INTO FUNCTIONAL MODULES

The CA3 subfield of the hippocampus has long been held as key to the brain’s ability to retrieve memories. Prominent theories posit that its recurrent network architecture forms the basis of a content-addressable memory system, wherein partial information is used to retrieve complete episodic traces. While the effect of recurrent connectivity on the online spatial coding characteristics of CA3 pyramidal cells has been extensively investigated, little is known of its contribution to offline memory retrieval in vivo. Using two-photon calcium imaging, we monitored the activity of proximal and distal CA3 pyramidal cell populations during active foraging and post-task resting periods in mice head-fixed under a virtual reality apparatus. Consistent with previous reports, higher recurrent connectivity in distal CA3 (close to CA2) was associated with increased representational stability, albeit at the cost of diminished ability to discriminate across disparate spatial contexts. Interestingly, in proximal CA3 (close to dentate gyrus), we noted subsets of neurons that spontaneously and simultaneously remapped during repeated navigation inside a persistent spatial context. These “remapping modules”, which appeared most prominently in proximal CA3, remapped arbitrarily and independently from one another, while other neurons remained stable throughout running lags. During rest, neuronal ensembles that participated in reactivation events consisted of the same member neurons as those that comprised remapping modules. Such reactivation events appeared to reinstate short trajectory segments in the previously explored environment. Altogether, our results suggest a functionally modular organization to CA3 populations, possibly governed by the degree of recurrent connectivity.