Postoperative loss of perineuronal nets in the hippocampal CA1 region results in memory consolidation deficits

Postoperative cognitive dysfunction (POCD) is a common postoperative neurological complication, with memory consolidation deficits being one of its prominent features. However, the mechanisms underlying postoperative memory consolidation deficits are still unclear. The perineuronal net (PNN) is a specialized extracellular matrix that predominantly surrounds parvalbumin (PV) interneurons and is closely associated with cognitive functions, including learning and memory. Theta oscillations in the hippocampal CA1 region are crucial for memory consolidation. However, the relationships among postoperative memory consolidation deficits, theta oscillation abnormalities, and PNNs remain unclear. The aim of this study was to investigate the role of PNNs in the CA1 region in postoperative memory consolidation deficits and theta oscillation abnormalities. The experiments revealed that, after anesthesia and surgery, the mice exhibited memory consolidation deficits, abnormal theta oscillations, and PNNs loss in the hippocampal CA1 region. Increasing the density of PNNs alleviated postoperative memory consolidation deficits and theta oscillation abnormalities. In contrast, normal mice treated with chondroitinase ABC (ChABC) to degrade PNNs presented a similar phenotype of postoperative memory consolidation deficits. Further investigations revealed that PNNs loss in surgical mice weakened the inhibitory function of PV interneurons. Increase the density of PNNs reversed these changes, while ChABC degradation of PNNs also weakened the inhibitory function of PV interneurons. Notably， PNNs loss after surgery was associated with increased microglial phagocytosis. In conclusion, the PNNs loss caused by increased microglial phagocytosis in the hippocampal CA1 region after surgery palys an important role in postoperative memory consolidation deficits and theta oscillation abnormalities, which is associated with the impaired function of PV interneurons. This study provides new theoretical insights and potential targets for preventing and treating postoperative memory consolidation deficits.