Silencing hippocampal CA2 reduces behavioral flexibility in spatial learning

Abstract

The hippocampus is a key structure involved in learning and remembering spatial information. However the extent to which hippocampal region CA2 is involved in these processes remains unclear. Here we show that chronically silencing dorsal CA2 impairs reversal learning in the Morris water maze. After platform relocation, CA2-silenced mice spent more time in the vicinity of the old platform location and less time in the new target quadrant. Accordingly, behavioral strategy analysis revealed increased perseverance in navigating to the old location during the first day and an increased use of non-spatial strategies during the second day of reversal learning. Confirming previous indirect indications, these results demonstrate that CA2 is recruited when mice must flexibly adapt their behavior as task contingencies change. We discuss how these findings can be explained by recent theories of CA2 function and outline testable predictions to understand the underlying neural mechanisms. Demonstrating a direct involvement of CA2 in spatial learning, this work lends further support to the notion that CA2 plays a fundamental role in hippocampal information processing.

Behavioral status modulates CA2 influence on hippocampal network dynamics

“…The fact that CA1 cells still displayed comparable rate coding properties following CA2 inhibition (Figure 3c) for the whole session, albeit with slower emergence and poorer stability in the temporal domain (Figure 3d,e), may explain the comparable population decoding performance in CA1 estimated by CNN network between the groups (Figure 4c). Crucially, the integration of these two results suggests the reliability and robustness of the novel CNN network and supports the hypothesis that CA2 might be recruited more during adaptive learning (Lehr et al, 2022).…”