Divergent neurocircuitry dissociates two components of the stress response: glucose mobilization and anxiety-like behavior

Xianglian Jia; Shanping Chen; Xulin Li; Sijue Tao; Juan Lai; Haoran Liu; Kang Huang; Ye Tian; Pengfei Wei; Fan Yang; Zhonghua Lu; Zuxin Chen; Xin-An Liu; Fuqiang Xu; Liping Wang

doi:10.1016/j.celrep.2022.111586

Divergent neurocircuitry dissociates two components of the stress response: glucose mobilization and anxiety-like behavior

Cell Rep. 2022 Nov 8;41(6):111586. doi: 10.1016/j.celrep.2022.111586.

Authors

Xianglian Jia¹, Shanping Chen², Xulin Li², Sijue Tao³, Juan Lai⁴, Haoran Liu⁴, Kang Huang⁴, Ye Tian², Pengfei Wei⁴, Fan Yang⁴, Zhonghua Lu⁴, Zuxin Chen⁴, Xin-An Liu⁴, Fuqiang Xu⁴, Liping Wang⁵

Affiliations

¹ Shenzhen Key Lab of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science, Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Center for Excellence in Brain Science and Intelligence Technology, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China; University of the Chinese Academy of Sciences, Beijing 100049, China; Shenzhen College of Advanced Technology, University of the Chinese Academy of Sciences, Shenzhen 518055, China.
² Shenzhen Key Lab of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science, Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Center for Excellence in Brain Science and Intelligence Technology, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China; University of the Chinese Academy of Sciences, Beijing 100049, China.
³ Wuhan Institute of Physics and Mathematics, Center for Excellence in Brain Science, Chinese Academy of Sciences, Wuhan 430071, China.
⁴ Shenzhen Key Lab of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science, Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Center for Excellence in Brain Science and Intelligence Technology, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China.
⁵ Shenzhen Key Lab of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science, Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Center for Excellence in Brain Science and Intelligence Technology, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, China. Electronic address: lp.wang@siat.ac.cn.

PMID: 36351404
DOI: 10.1016/j.celrep.2022.111586

Abstract

Stress is a risk factor for emotion and energy metabolism disorders. However, the neurocircuitry mechanisms for emotion initiation and glucose mobilization underlying stress responses are unclear. Here we demonstrate that photoactivation of Gad2+ projection from the anterior bed nucleus of the stria terminalis (aBNST) to the arcuate nucleus (ARC) induces anxiety-like behavior as well as acute hyperglycemia. Photoinhibition of the circuit is anxiolytic and blocks hyperglycemia induced by restraint stress. Pharmacogenetic inhibition of the ARC^Gad2+→raphe obscurus nucleus (ROb) and photoactivation of the aBNST^Gad2+→ARC circuits simultaneously leads to significant hypoglycemia and anxiety-like behavior. Pharmacogenetic inhibition of the ARC^Gad2+→nucleus of the solitary tract (NTS) whilst photoactivation of the aBNST^Gad2+→ARC circuit only induces hyperglycemia. Our results reveal that the aBNST^Gad2+→ARC^Gad2+→ROb circuit is recruited for the stress response of rapid glucose mobilization and the aBNST^Gad2+→ARC^Gad2+→NTS circuit for behavioral symptoms of stress response. This study identifies a possible general strategy for neurocircuitry structural organization dealing with multiple organs involved in responses, with potential therapeutic targets for emotion and energy metabolism disorders underlying psychiatric disorders.

Keywords: ARC; CP: Neuroscience; NTS; ROb; aBNST; anxiety-like behavior; glucose.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anxiety / metabolism
Arcuate Nucleus of Hypothalamus
Glucose / metabolism
Humans
Hyperglycemia* / metabolism
Septal Nuclei* / physiology

Substances

Glucose