A Distinct Subpopulation of Extended Amygdala Neurons Drives Food Intake
Biol Psychiatry Glob Open Sci. 2026 Apr 24;6(4):100744. doi: 10.1016/j.bpsgos.2026.100744. eCollection 2026 Jul.
ABSTRACT
BACKGROUND: Neurons 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 Vipr2-expressing ovBNST neurons using chemogenetics, immunohistochemistry, and viral circuit mapping.
METHODS: We used stimulatory hM3Dq DREADDs (designer receptors exclusively activated by designer drugs) to chemogenetically activate ovBNST Vipr2 neurons and assess effects on food intake. cFos activation was quantified in Vipr2-tdTomato reporter mice following several feeding-related manipulations, including food restriction (FR). Vasoactive intestinal peptide (VIP) innervation of the ovBNST was analyzed under FR conditions. Given previous reports of reduced food intake following stimulation of ovBNST neurons expressing protein kinase C delta (PKCδ), immunostaining was performed to examine the overlap between Vipr2- and PKCδ-expressing neuronal populations. Cre-dependent anterograde viral tracing was used to map projections of ovBNST Vipr2 neurons.
RESULTS: We found that chemogenetic activation of ovBNST Vipr2 neurons significantly increased food intake. Additionally, FR robustly activated ovBNST Vipr2 neurons as indicated by increased cFos expression, and FR was associated with decreased VIP innervation of the ovBNST. Immunostaining revealed that Vipr2 and PKCδ mark largely non-overlapping neuronal subpopulations in the ovBNST, consistent with their opposing effects on feeding. Finally, Cre-dependent anterograde viral tracing showed that ovBNST Vipr2 neurons project prominently to the parasubthalamic nucleus and paraventricular nucleus of the hypothalamus, both key feeding-related regions.
CONCLUSIONS: Together, these results identify ovBNST Vipr2 neurons as a functionally distinct BNST subpopulation that promotes feeding, is activated by FR, and links ovBNST neuropeptide signaling to hypothalamic feeding centers.
PMID:42293405 | PMC:PMC13260202 | DOI:10.1016/j.bpsgos.2026.100744