Two parallel medial prefrontal cortex-amygdala pathways mediate memory deficits via glutamatergic projection in surgery mice
Xiao-Yu Sun,
Le Liu,
Yu-Tong Song,
Tong Wu,
Teng Zheng,
Jing-Ru Hao,
Jun-Li Cao,
Can Gao
Affiliations
Xiao-Yu Sun
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Department of Anesthesiology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road, Shanghai 200127, China
Le Liu
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
Yu-Tong Song
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
Tong Wu
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
Teng Zheng
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
Jing-Ru Hao
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
Jun-Li Cao
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China
Can Gao
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China; Corresponding author
Summary: The neural circuit mechanisms underlying postoperative cognitive dysfunction (POCD) remain elusive. We hypothesized that projections from the medial prefrontal cortex (mPFC) to the amygdala are involved in POCD. A mouse model of POCD in which isoflurane (1.5%) combined with laparotomy was used. Virally assisted tracing techniques were used to label the relevant pathways. Fear conditioning, immunofluorescence, whole-cell patch-clamp recordings, and chemogenetic and optogenetic techniques were applied to investigate the role of mPFC-amygdala projections in POCD. We find that surgery impairs memory consolidation but not retrieval of consolidated memories. In POCD mice, the glutamatergic pathway from the prelimbic cortex to the basolateral amygdala (PL-BLA) shows reduced activity, whereas the glutamatergic pathway from the infralimbic cortex to the basomedial amygdala (IL-BMA) shows enhanced activity. Our study indicates that the hypoactivity in the PL-BLA pathway interrupts memory consolidation, whereas the hyperactivity in the IL-BMA promotes memory extinction, in POCD mice.
