Divergent input patterns to the central lateral amygdala play a duet in fear memory formation
Jing-hua Gao,
Yue-ying Liu,
Hui-xiang Xu,
Ke Wu,
Le-le Zhang,
Peng Cheng,
Xiao-han Peng,
Jun-li Cao,
Rong Hua,
Yong-mei Zhang
Affiliations
Jing-hua Gao
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou 221002, Jiangsu, China; Department of Anesthesiology, The Yancheng Clinical College of Xuzhou Medical University, The First People’s Hospital of Yancheng, Yancheng 224008, Jiangsu, China
Yue-ying Liu
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China
Hui-xiang Xu
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China
Ke Wu
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China
Le-le Zhang
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China
Peng Cheng
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China
Xiao-han Peng
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China
Jun-li Cao
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; Corresponding author
Rong Hua
Department of Emergency, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, Jiangsu, China; Corresponding author
Yong-mei Zhang
NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China; Corresponding author
Summary: Somatostatin (SOM)-expressing neurons in the central lateral amygdala (CeL) are responsible for fear memory learning, but the circuit and molecular mechanisms underlying this biology remain elusive. Here, we found that glutamatergic neurons in the lateral parabrachial nucleus (LPB) directly dominated the activity of CeLSOM neurons, and that selectively inhibiting the LPBGlu→CeLSOM pathway suppressed fear memory acquisition. By contrast, inhibiting CeL-projecting glutamatergic neurons in the paraventricular thalamic nucleus (PVT) interfered with consolidation-related processes. Notably, CeLSOM-innervating neurons in the LPB were modulated by presynaptic cannabinoid receptor 1 (CB1R), and knock down of CB1Rs in LPB glutamatergic neurons enhanced excitatory transmission to the CeL and partially rescued the impairment in fear memory induced by CB1R activation in the CeL. Overall, our study reveals the mechanisms by which CeLSOM neurons mediate the formation of fear memories during fear conditioning in mice, which may provide a new direction for the clinical research of fear-related disorders.
