Postoperative cognitive dysfunction (POCD) is a serious and underrecognized complication in older surgical patients. This study in aged mice shows that surgery suppresses a key brain circuit — cholinergic neurons projecting from the medial septum to the hippocampal dentate gyrus — reducing acetylcholine release and shutting down the birth of new neurons. When researchers restored signaling along this pathway, either with the drug galantamine or chemogenetic activation, memory deficits reversed and neurogenesis recovered. The findings pinpoint a specific neural circuit as a causal driver of POCD, suggesting that targeting cholinergic signaling in the hippocampus before or after surgery could protect cognitive function in elderly patients.
