Silencing hippocampal CA2 reduces behavioral flexibility in spatial learning

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.

Automated summary

The hippocampus, particularly the CA2 region, is involved in learning and remembering spatial information. Silencing the CA2 region impairs reversal learning in mice, as they spend more time near the old platform location and show increased use of non-spatial strategies during reversal learning. These findings support the idea that CA2 plays a fundamental role in flexible behavior adaptation and provide insights into the neural mechanisms underlying hippocampal information processing.