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

doi:10.1016/j.isci.2024.110886

Divergent input patterns to the central lateral amygdala play a duet in fear memory formation

iScience. 2024 Sep 4;27(10):110886. doi: 10.1016/j.isci.2024.110886. eCollection 2024 Oct 18.

Authors

Jing-Hua Gao^{1

2}, Yue-Ying Liu^{1

3

4}, Hui-Xiang Xu^{1

3

4}, Ke Wu^{1

3

4}, Le-le Zhang^{1

3

4}, Peng Cheng^{1

3

4}, Xiao-Han Peng^{1

3

4}, Jun-Li Cao^{1

3

4}, Rong Hua⁵, Yong-Mei Zhang^{1

3

4}

Affiliations

¹ NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou 221002, Jiangsu, China.
² Department of Anesthesiology, The Yancheng Clinical College of Xuzhou Medical University, The First People's Hospital of Yancheng, Yancheng 224008, Jiangsu, China.
³ Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China.
⁴ Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221002, Jiangsu, China.
⁵ Department of Emergency, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, Jiangsu, China.

Abstract

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 CeL^SOM neurons, and that selectively inhibiting the LPB^Glu→CeL^SOM pathway suppressed fear memory acquisition. By contrast, inhibiting CeL-projecting glutamatergic neurons in the paraventricular thalamic nucleus (PVT) interfered with consolidation-related processes. Notably, CeL^SOM-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 CeL^SOM 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.

Keywords: Molecular neuroscience; Neuroscience; Sensory neuroscience.