Dataset Information

Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety.

ABSTRACT: Dysregulated prefrontal control over amygdala is engaged in the pathogenesis of psychiatric diseases including depression and anxiety disorders. Here we show that, in a rodent anxiety model induced by chronic restraint stress (CRS), the dysregulation occurs in basolateral amygdala projection neurons receiving mono-directional inputs from dorsomedial prefrontal cortex (dmPFC?BLA PNs) rather than those reciprocally connected with dmPFC (dmPFC?BLA PNs). Specifically, CRS shifts the dmPFC-driven excitatory-inhibitory balance towards excitation in the former, but not latter population. Such specificity is preferential to connections made by dmPFC, caused by enhanced presynaptic glutamate release, and highly correlated with the increased anxiety-like behavior in stressed mice. Importantly, low-frequency optogenetic stimulation of dmPFC afferents in BLA normalizes the enhanced prefrontal glutamate release onto dmPFC?BLA PNs and lastingly attenuates CRS-induced increase of anxiety-like behavior. Our findings thus reveal a target cell-based dysregulation of mPFC-to-amygdala transmission for stress-induced anxiety.

SUBMITTER: Liu WZ

PROVIDER: S-EPMC7203160 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety.

Liu Wei-Zhu WZ Zhang Wen-Hua WH Zheng Zhi-Heng ZH Zou Jia-Xin JX Liu Xiao-Xuan XX Huang Shou-He SH You Wen-Jie WJ He Ye Y Zhang Jun-Yu JY Wang Xiao-Dong XD Pan Bing-Xing BX

Nature communications 20200506 1

Dysregulated prefrontal control over amygdala is engaged in the pathogenesis of psychiatric diseases including depression and anxiety disorders. Here we show that, in a rodent anxiety model induced by chronic restraint stress (CRS), the dysregulation occurs in basolateral amygdala projection neurons receiving mono-directional inputs from dorsomedial prefrontal cortex (dmPFC→BLA PNs) rather than those reciprocally connected with dmPFC (dmPFC↔BLA PNs). Specifically, CRS shifts the dmPFC-driven exc ...[more]

PMID: 32376858

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Project description:BackgroundAnxiety and stress reactivity are risk factors for the development of affective disorders. However, the behavioral and neurocircuit mechanisms that potentiate maladaptive emotion regulation are poorly understood. Neuroimaging studies have implicated the amygdala and dorsolateral prefrontal cortex (DLPFC) in emotion regulation, but how anxiety and stress alter their context-specific causal circuit interactions is not known. Here, we use computational modeling to inform affective pathophysiology, etiology, and neurocircuit targets for early intervention.MethodsForty-five children (10-11 years of age; 25 boys) reappraised aversive stimuli during functional magnetic resonance imaging scanning. Clinical measures of anxiety and stress were acquired for each child. Drift-diffusion modeling of behavioral data and causal circuit analysis of functional magnetic resonance imaging data, with a National Institute of Mental Health Research Domain Criteria approach, were used to characterize latent behavioral and neurocircuit decision-making dynamics driving emotion regulation.ResultsChildren successfully reappraised negative responses to aversive stimuli. Drift-diffusion modeling revealed that emotion regulation was characterized by increased initial bias toward positive reactivity during viewing of aversive stimuli and increased drift rate, which captured evidence accumulation during emotion evaluation. Crucially, anxiety and stress reactivity impaired latent behavioral dynamics associated with reappraisal and decision making. Anxiety and stress increased dynamic casual influences from the right amygdala to DLPFC. In contrast, DLPFC, but not amygdala, reactivity was correlated with evidence accumulation and decision making during emotion reappraisal.ConclusionsOur findings provide new insights into how anxiety and stress in children impact decision making and amygdala-DLPFC signaling during emotion regulation, and uncover latent behavioral and neurocircuit mechanisms of early risk for psychopathology.

Dataset Information

Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety.

Publications

Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety.

Similar Datasets

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