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bioRxiv · 10.1101/2025.11.07.685941

A Distinct Subpopulation of Extended Amygdala Neurons Drives Food Intake

Kandil, I. F.·Rogers, E. T.·Morningstar, A. R.·Giardino, W. J.
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Abstract

BackgroundNeurons in the oval subnucleus of the bed nucleus of the stria terminalis (ovBNST) integrate stress and reward signals to regulate motivated behaviors, including food consumption. However, the contribution of specific ovBNST neuronal subpopulations remains poorly understood. Here, we investigated vasoactive intestinal peptide receptor 2 (Vipr2) expressing ovBNST neurons using chemogenetics, immunohistochemistry, and viral circuit mapping. Methods and ResultsUsing stimulatory hM3Dq designer receptors exclusively activated by designer drugs (DREADDs), we found that chemogenetic activation of ovBNSTVipr2neurons significantly increased food intake. We then quantified cFos activation in Vipr2-tdTomato reporter mice following several unique feeding-related manipulations, finding that food restriction (FR) robustly activated ovBNSTVipr2 neurons. Further analysis revealed decreased vasoactive intestinal peptide (VIP) innervation of the ovBNST following FR, in which reduced VIP expression was significantly associated with greater ovBNSTVipr2 cFos activation. Given previous reports of reduced food intake following stimulation of ovBNST neurons expressing protein kinase C delta (PKC{delta}), we used immunostaining to uncover that Vipr2 and PKC{delta} mark largely non-overlapping ovBNST neuronal subpopulations, aligning with their opposing effects on food intake. Finally, Cre-dependent anterograde viral tracing revealed that ovBNSTVipr2 neurons project prominently to the parasubthalamic nucleus (PSTN) and paraventricular nucleus of the hypothalamus (PVN), two feeding-related regions. ConclusionsTogether, these results identify ovBNSTVipr2neurons as a functionally distinct BNST subpopulation that promotes feeding, is activated by food restriction, and links ovBNST neuropeptide signaling to hypothalamic feeding centers.

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Kandil, I. F., Rogers, E. T., Morningstar, A. R., Giardino, W. J.. 2025-11-10. A Distinct Subpopulation of Extended Amygdala Neurons Drives Food Intake. https://doi.org/10.1101/2025.11.07.685941

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