Sgk1 upregulation in hippocampus-projecting amygdala neurons underlies the delayed onset of PTSD-like avoidance behavior.

Overview

1. School of Life Science, Nanchang University, Nanchang, China
2. School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, Nanchang, China
3. Jiangxi Province Key Laboratory of Brain Science and Brain Health, Institute of Biomedical Innovation, Jiangxi Medical College, Nanchang University, Nanchang, China
4. Department of Pathology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
5. Department of Neurology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
6. Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China

Abstract

Excessive avoidance is a core symptom of post-traumatic stress disorder (PTSD), yet its underlying circuit mechanisms remain poorly understood. Here, using a mouse model of PTSD induced by inescapable footshock, we observed a delayed and prolonged increase in avoidance behavior associated with selective activation of basolateral amygdala (BLA) projection neurons (PNs) targeting ventral hippocampus (BLA→vHPC PNs), but not nucleus accumbens, in both sexes. This projection-specific activation results from enhanced neuronal excitability and excitatory transmission driven by glucocorticoid receptor (GR) signaling. Among the cascade of GR signaling molecules, we identified serum- and glucocorticoid-regulated kinase 1 (Sgk1) as a key downstream mediator linking stress exposure to the hyperactivation of BLA→vHPC PNs and PTSD-like avoidance behavior. Manipulating Sgk1 expression bidirectionally regulates neuronal activity and susceptibility to stress-induced avoidance. These findings underscore the critical role of projection-specific upregulation of Sgk1 in BLA PNs in the pathogenesis of PTSD-like avoidance behavior.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

No file of the authors' code could be read here: it is described below, and read at its source.

Code availability

The MATLAB-based software package used for analyzing the fiber photometry data in this study was developed by ThinkerTech Nanjing BioScience Inc. and is publicly available via the Zenodo repository at: 10.5281/zenodo.15009455.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• figshare:28417763, at figshare; found in DataCite

Data availability

All data generated and analyzed during this study are included in this article and its supplementary information files. The datasets have also been deposited in the Figshare repository under the accession link 10.6084/m9.figshare.28417763. Source data are provided with this paper.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 3 keywords, 18 MeSH terms, 2 funders, 77 references.

Cite

This paper

Zou, J.-X., Liu, W.-Z., Li, Y.-Q., Li, Y.-Y., You, W.-J., Pan, H.-Q., Wang, C.-Y., Zhang, W.-H., & Pan, B.-X. (2026). Sgk1 upregulation in hippocampus-projecting amygdala neurons underlies the delayed onset of PTSD-like avoidance behavior. Nature communications, 17(1), 4683. https://doi.org/10.1038/s41467-026-71129-0

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