Acute Stress Drives Adaptive Anxiety via Excitatory-Inhibitory Imbalance in the Prefrontal-Amygdala Circuit in Male Mice
Jia‑Xin Zou1,2,7 · En Cao1 · Zhi‑Hao Wang1,2 · Rui Han3 · Xing‑Yan Lu1 · Cheng‑Yuan Huang1,2 · Xia Qin4 · Wei‑Zhu Liu1,6 · Wen‑Hua Zhang1,2,5 · Bing‑Xing Pan1,2
1 Department of Pathology, The First Affiliated Hospital and Institute of Biomedical Innovation, School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
2 Jiangxi Province Key Laboratory of Brain Science and Brain Health, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
3 Queen Mary School, Nanchang University, Nanchang 330001, China
4 Jiangsu Provincial Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou 221004, China
5 Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
6 Jiangxi Province Key Laboratory of Precision Pathology and Intelligent Diagnosis, Jiangxi Medical College, Nanchang University, Nanchang 330031, China
7 Postdoctoral Innovation Practice Base, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330036, China
Abstract
Acute stress rapidly reshapes brain function to promote adaptive behavioral responses. Although dysfunction of the medial prefrontal cortex (mPFC)-amygdala circuit is well established in chronic stress-related anxiety, its role in acute adaptive anxiety remains unresolved. Here, using an acute restraint stress (ARS) model in male mice, we identified temporally restricted, projection-specific recruitment of dorsomedial prefrontal cortex (dmPFC) circuitry that regulates acute anxiety-like behavior. ARS selectively increased the activity of dmPFC projection neurons (PNs) at 2 h, but not 24 h post-stress, with minimal ventromedial prefrontal cortex engagement. This transient activation was confined to basolateral amygdala-projecting neurons (dmPFC→BLA PNs) in layer II/III and layer V. Mechanistically, ARS enhanced excitatory synaptic transmission without altering inhibition, shifting the excitation-inhibition balance toward excitation in dmPFC→BLA PNs. Functionally, inhibiting this circuit attenuated ARS-induced anxiety-like behavior, whereas activating it in unstressed mice recapitulated an anxiogenic state.
Keywords
Acute stress; Anxiety; Prefrontal cortex; Neural circuit; Excitatory-inhibitory balance
