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The amygdala, a key target for chronic stress, forms the hub of the brain’s emotional circuits with the medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC). The structural and functional remodeling of the amygdala, especially the basolateral amygdala (BLA), caused by chronic stress is closely related to attendant changes in mood disorders such as anxiety disorders. Our previous study found that chronic stress differentially regulated BLA projection neurons (PNs) in different circuits, as evidenced by the fact that spine density and glutamatergic signaling only in BLA PNs targeting vHPC (BLA→vHPC PNs) were remodeled by chronic restraint stress (CRS), whereas BLA PNs targeting mPFC (BLA→mPFC PNs) and nucleus accumbens (BLA→NAc PNs) were not markedly altered. However, the underlying mechanisms are unclear. These BLA PNs integrated in different neural circuits are in an almost-the-same microenvironment, but triggered different reactions to stress, suggesting that they may have different signal receiving or transmitting mechanisms. Considering the critical role of glucocorticoids in the modulation of brain structure and function by stress, we hypothesize that glucocorticoid receptor (GR) may be a potential mediator of the differential regulation of BLA neurons by chronic stress. In this study, we sought to clarify whether the expression levels of GR on BLA PNs in different circuits and their response patterns to CRS are different. And the results showed that CRS significantly enhanced the GR expression of BLA→vHPC PNs, but had no obvious effect on the GR expression of BLA→mPFC PNs and BLA→NAc PNs. Moreover, the increase of corticosterone concentration in mice caused by prolonged stress only selectively caused the elevated response of GR in BLA→vHPC PNs. Taken together, our findings hint that the GR may be a potential and essential mediator of chronic stress-caused differential regulation on BLA PN.


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Glucocorticoid receptor, a potential mediator of differential regulation on amygdala neurons by chronic stress

Show Author's information Yuan-Pei Zhang1Chen-Ming Zhong1Long-Xin Wu2Bing-Xing Pan1Jun-Yu Zhang1( )
Laboratory of Fear and Anxiety Disorders, Institute of Life Science, Nanchang University, Nanchang 330031, China
School of Life Sciences, Nanchang University, Nanchang 330031, China

Abstract

The amygdala, a key target for chronic stress, forms the hub of the brain’s emotional circuits with the medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC). The structural and functional remodeling of the amygdala, especially the basolateral amygdala (BLA), caused by chronic stress is closely related to attendant changes in mood disorders such as anxiety disorders. Our previous study found that chronic stress differentially regulated BLA projection neurons (PNs) in different circuits, as evidenced by the fact that spine density and glutamatergic signaling only in BLA PNs targeting vHPC (BLA→vHPC PNs) were remodeled by chronic restraint stress (CRS), whereas BLA PNs targeting mPFC (BLA→mPFC PNs) and nucleus accumbens (BLA→NAc PNs) were not markedly altered. However, the underlying mechanisms are unclear. These BLA PNs integrated in different neural circuits are in an almost-the-same microenvironment, but triggered different reactions to stress, suggesting that they may have different signal receiving or transmitting mechanisms. Considering the critical role of glucocorticoids in the modulation of brain structure and function by stress, we hypothesize that glucocorticoid receptor (GR) may be a potential mediator of the differential regulation of BLA neurons by chronic stress. In this study, we sought to clarify whether the expression levels of GR on BLA PNs in different circuits and their response patterns to CRS are different. And the results showed that CRS significantly enhanced the GR expression of BLA→vHPC PNs, but had no obvious effect on the GR expression of BLA→mPFC PNs and BLA→NAc PNs. Moreover, the increase of corticosterone concentration in mice caused by prolonged stress only selectively caused the elevated response of GR in BLA→vHPC PNs. Taken together, our findings hint that the GR may be a potential and essential mediator of chronic stress-caused differential regulation on BLA PN.

Keywords:

chronic stress, basolateral amygdala, glucocorticoid receptor, neural circuits, differential regulation
Received: 17 July 2022 Revised: 19 September 2022 Accepted: 17 October 2022 Published: 30 November 2022
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Publication history

Received: 17 July 2022
Revised: 19 September 2022
Accepted: 17 October 2022
Published: 30 November 2022

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© The Author(s) 2022

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (Nos. 81960257 and 81503079) and the Special Funds for Central Government to Guide Local Scientific and Technological Development (No. 20202ZDB01015).

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