Retrosplenial perineuronal nets support hippocampal-cortical coupling and spatial memory recall

The retrosplenial cortex (RSC) integrates hippocampal output with cortical networks to support spatial memory. In the RSC, inhibitory parvalbumin interneurons regulate local circuit dynamics and are enwrapped by perineuronal nets (PNNs), which stabilize neuronal activity and connectivity. However, the contribution of cortical PNNs to interregional communication remains unclear. Here, we examine how PNN degradation in the granular RSC (RSCg) affects spatial memory recall and neuronal activity in the RSCg and dorsal CA1 (dCA1). PNN degradation impairs spatial memory recall and increases c-Fos+ and c-Fos+PNN+ cell counts in RSCg. Electrophysiological recordings reveal disrupted oscillatory activity, with reduced gamma oscillations and theta-gamma coupling in RSCg and diminished theta oscillations in dCA1. This is accompanied by decreased interregional gamma coupling and impaired functional connectivity of excitatory spike pairs between dCA1 and RSCg. These findings indicate that PNNs stabilize coordinated dynamics required for hippocampal-RSC communication and memory retrieval.