Proximodistal Segregation of Nonspatial Information in CA3: Preferential Recruitment of a Proximal CA3-Distal CA1 Network in Nonspatial Recognition Memory

Abstract

A prevailing view in memory research is that CA3 principally supports spatial processes. However, few studies have investigated the contribution of CA3 to nonspatial memory function. Interestingly, the proximal part of CA3 (close to the dentate gyrus) predominantly projects to distal CA1 (away from the dentate gyrus), which preferentially processes nonspatial information. Moreover, the cytoarchitecture and connectivity patterns in the proximal and distal parts of CA3 strongly differ, suggesting a functional segregation in this area. Here, we tested whether CA3 is recruited during nonspatial recognition memory, and whether nonspatial information is differentially represented along the proximodistal axis of CA3. Furthermore, we investigated whether the pattern of activation within CA3 would mirror that of CA1. We used a high-resolution imaging technique specifically designed to analyze brain activity in distant areas that is based on the detection of the expression of the immediate-early gene Arc, used as a marker of neuronal activation. We showed that proximal CA3 is strongly recruited during a nonspatial delayed nonmatching-to-sample recognition memory task in rats, while distal CA3 is not. In addition, distal CA1 was more activated than proximal CA1 in the same task. These findings suggest a functional segregation of CA3 that mirrors that of CA1, and potentially indicate the existence of a proximal CA3-distal CA1 hippocampal subnetwork that would preferentially process nonspatial information during recognition memory.