Amygdala GABA Neurons: Gatekeepers of Stress and Reproduction

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Detalles Bibliográficos
Publicado en:bioRxiv (Feb 9, 2025)
Autor principal: Yu, Junru
Otros Autores: Farjami, Saeed, Nechyporenko, Kateryna, Xiao Feng Li, Yaseen, Hafsa, Lin, Yanyan, Ye, Jinbin, Hollings, Owen, De Burgh, Ross, O'byrne, Kevin T, Tsaneva-Atanasova, Krasimira, Margaritis Voliotis
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Cold Spring Harbor Laboratory Press
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LEADER 00000nab a2200000uu 4500
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022 |a 2692-8205 
024 7 |a 10.1101/2025.01.06.631361  |2 doi 
035 |a 3152304573 
045 0 |b d20250209 
100 1 |a Yu, Junru 
245 1 |a Amygdala GABA Neurons: Gatekeepers of Stress and Reproduction 
260 |b Cold Spring Harbor Laboratory Press  |c Feb 9, 2025 
513 |a Working Paper 
520 3 |a Stress can disrupt menstrual cycles, cause infertility, and lead to other reproductive disorders. The posterodorsal medial amygdala (MePD) processes stress signals and regulates the gonadotropin-releasing hormone (GnRH) pulse generator through GABAergic inhibitory projections to the hypothalamus. However, how stress is processed in the MePD - especially involving its dense GABAergic and Urocortin-3 (UCN3) neurons - remains poorly understood. In this study, we combine in vivo GRadient-INdex (GRIN) lens mini-endoscopic calcium imaging (to track neuronal activity), optogenetics, clustering analysis, and computational modeling to investigate MePD circuitry. Our findings reveal two anti-correlated GABAergic sub-populations in the MePD that dictate responses to both UCN3 neuron stimulation and restraint stress. Our computational modeling suggests that mutual inhibition between these GABAergic groups drives this anti-correlated activity and predicts how these interactions shape downstream responses to stimulation of GABAergic and UCN3 neurons. We test these predictions using optogenetics and confirm that GABAergic neurons operate downstream of the UCN3 population, playing a crucial role in transmitting UCN3 signals to regulate luteinizing hormone (LH) pulse frequency. Our study is the first to show how GABAergic neurons in the amygdala mediate stress effects on reproductive health, uncovering key neural mechanisms linking emotional and reproductive functions.Competing Interest StatementThe authors have declared no competing interest.Footnotes* The manuscript has been updated: Figures 1-6 have been modified, Results and Discussion sections have been expanded. We expanded Supplementary Information file. 
653 |a Hypothalamus 
653 |a Signal processing 
653 |a Amygdala 
653 |a Optics 
653 |a Neurons 
653 |a Luteinizing hormone 
653 |a Neurogenesis 
653 |a Calcium signalling 
653 |a Infertility 
653 |a Pituitary (anterior) 
653 |a γ-Aminobutyric acid 
653 |a Arcuate nucleus 
653 |a Gonadotropins 
653 |a Gonadotropin-releasing hormone 
653 |a Calcium imaging 
653 |a Information processing 
653 |a Population studies 
653 |a Genetics 
653 |a Urocortin 
653 |a Reproductive health 
700 1 |a Farjami, Saeed 
700 1 |a Nechyporenko, Kateryna 
700 1 |a Xiao Feng Li 
700 1 |a Yaseen, Hafsa 
700 1 |a Lin, Yanyan 
700 1 |a Ye, Jinbin 
700 1 |a Hollings, Owen 
700 1 |a De Burgh, Ross 
700 1 |a O'byrne, Kevin T 
700 1 |a Tsaneva-Atanasova, Krasimira 
700 1 |a Margaritis Voliotis 
773 0 |t bioRxiv  |g (Feb 9, 2025) 
786 0 |d ProQuest  |t Biological Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3152304573/abstract/embedded/L8HZQI7Z43R0LA5T?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3152304573/fulltextPDF/embedded/L8HZQI7Z43R0LA5T?source=fedsrch 
856 4 0 |3 Full text outside of ProQuest  |u https://www.biorxiv.org/content/10.1101/2025.01.06.631361v2