Abstract
Stress can disrupt menstrual cycles, impair fertility and cause reproductive disfunction. The posterodorsal medial amygdala (MePD) integrates stress signals and regulates the gonadotropin-releasing hormone (GnRH) pulse generator through a dense network of GABA and Urocortin-3 (UCN3) neurons, yet the mechanisms underlying the circuitry remain poorly understood. Here, we combine in vivo mini-endoscopic calcium imaging, optogenetics, clustering analysis, and computational modeling to investigate the MePD circuitry in female mice. We uncover two anti-correlated GABA subpopulations in the MePD that are involved in the response to restraint stress and UCN3 neuron stimulation. Computational modeling suggests that mutual inhibition between these GABA groups drives their anti-correlated activity and predicts how these interactions shape downstream responses to stimulation of GABA and UCN3 neurons. In vivo optogenetics confirms that GABA neurons are critical for transmitting UCN3 signals to regulate luteinizing hormone (LH) pulse frequency. Together, our findings reveal amygdala GABAergic circuit mechanisms that mediate stress effects on reproductive health, linking emotional processing and neuroendocrine control.
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Data availability
The main data supporting the results in this study are available within the paper and its Supplementary Information. Any additional requests for information can be directed to and will be fulfilled by the corresponding authors. Source data are provided with this paper. Source data are available at Figshare44 (https://doi.org/10.24378/exe.31021447). Source data are provided with this paper for reproducing all Figures in the manuscript and Supplementary Information. Source data are provided with this paper.
Code availability
The code for reproducing the data analysis (Python™), mathematical modeling (MATLAB™), and figure generation for both the main text and Supplementary information, along with the datasets used in the analysis, is publicly available at Figshare45(https://doi.org/10.24378/exe.31018072) or in Github repository (https://github.com/mv-kr/MePD_GABA).
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Acknowledgements
We thank Sumi Mathew for her technical support with genotyping mice. S.F., M.V., K.T.A., K.T.O., X.F.L. gratefully acknowledge the financial support of BBSRC via grants BB/W005913/1 (KCL), BB/W005883/1 (Exeter) and BB/S019979/1. K.T.A. gratefully acknowledges the financial support of the EPSRC via grant EP/T017856/. For the purpose of open access, the author has applied a ‘Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.
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J.Y. contributed data acquisition and data analysis, S.F. contributed data analysis, K.N. contributed modeling, M.V. contributed managing data analysis, X.F.L. contributed managing data acquisition and analysis, H.Y. contributed data acquisition, Y.L. contributed data acquisition, J.Y. contributed data acquisition, O.H. contributed data acquisition, R.D.B. contributed data acquisition, B.S. contributed data acquisition, K.T.O., K.T.A., X.F.L., and M.V. contributed to managing the project. All authors contributed to writing the manuscript.
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Yu, J., Farjami, S., Nechyporenko, K. et al. The role of amygdala GABA neurons in controlling stress and reproduction in female mice. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70364-9
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DOI: https://doi.org/10.1038/s41467-026-70364-9
