Spatial information is preferentially processed by the distal part of CA3: implication for memory retrieval.

For the past decades, CA3 was considered as a single functional entity. However, strong differences between the proximal (close to the dentate gyrus) and the distal (close to CA2) parts of CA3 in terms of connectivity patterns, gene expression and electrophysiological properties suggest that it is not the case. We recently showed that proximal CA3 (together with distal CA1) preferentially deals with non-spatial information [1]. In contrast to proximal CA3, distal CA3 mainly receives and predominantly projects to spatially tuned areas. Here, we tested if distal CA3 preferentially processes spatial information, which would suggest a segregation of the spatial information along the proximodistal axis of CA3. We used a high-resolution imaging technique based on the detection of the expression of the immediate-early gene Arc, commonly used to map activity in the medial temporal lobe. We showed that distal CA3 is strongly recruited in a newly designed delayed nonmatching-to-location task with high memory demands in rats, while proximal CA3 is not. These results indicate a functional segregation of CA3 that mirrors the one reported in CA1, and suggest the existence of a distal CA3- proximal CA1 spatial subnetwork. These findings bring further evidence for the existence of 'specialized' spatial and non-spatial subnetworks segregated along the proximodistal axis of the hippocampus and put forward the 'segregated' view of information processing in the hippocampus as a reasonable alternative to the well-accepted 'integrated' view, according to which spatial and non-spatial information are systematically integrated in the hippocampus to form episodic memory.