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

• DOI: 10.1016/j.celrep.2022.111586
• Publication Date: 2022-11-08T16:02:28Z
• Authors: 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
• Keywords: 0301 basic medicine; 0303 health sciences; 03 medical and health sciences; Glucose; Hyperglycemia; Arcuate Nucleus of Hypothalamus; Humans; Septal Nuclei; Anxiety

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 ARCGad2+→raphe obscurus nucleus (ROb) and photoactivation of the aBNSTGad2+→ARC circuits simultaneously leads to significant hypoglycemia and anxiety-like behavior. Pharmacogenetic inhibition of the ARCGad2+→nucleus of the solitary tract (NTS) whilst photoactivation of the aBNSTGad2+→ARC circuit only induces hyperglycemia. Our results reveal that the aBNSTGad2+→ARCGad2+→ROb circuit is recruited for the stress response of rapid glucose mobilization and the aBNSTGad2+→ARCGad2+→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.