{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:18:20Z","timestamp":1785403100298,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,23]]},"group-title":"Neuroscience","reference-count":43,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["DK136810"],"award-info":[{"award-number":["DK136810"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK138131"],"award-info":[{"award-number":["DK138131"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DK138755"],"award-info":[{"award-number":["DK138755"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"publisher"}]},{"award":["DA049924"],"award-info":[{"award-number":["DA049924"]}],"id":[{"id":"https:\/\/ror.org\/00fq5cm18","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Washington University Nutrition Obesity Research Center Pilot Award Program"},{"name":"Washington University Diabetes Research Center Pilot Award Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,23]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  Food intake is governed by two interacting drives. The homeostatic hunger drive regulates food intake to fulfill caloric needs while the hedonic drive promotes intake of palatable foods outside of caloric need. It is unclear which neural substrates can control the hedonic drive and thereby reduce overeating of palatable foods and associated obesity. Here, we show that ventral pallidal GABAergic neurons (VP\n                  <jats:sup>GABA<\/jats:sup>\n                  ) preferentially control hedonic feeding and are necessary for diet-induced obesity in mice. Stimulating VP\n                  <jats:sup>GABA<\/jats:sup>\n                  neurons drove robust consumption of high-fat diet and liquids, but not regular laboratory chow. Despite driving intake of palatable foods, VP\n                  <jats:sup>GABA<\/jats:sup>\n                  neurons are relatively insensitive to homeostatic signals \u2013 they express few hunger-hormone receptors and are not activated by ghrelin administration or fasting. Single-cell calcium imaging revealed stronger engagement of VP\n                  <jats:sup>GABA<\/jats:sup>\n                  neurons during long vs short feeding bouts, suggesting control over bout duration, which has been linked to palatability. This was confirmed with closed-loop optogenetic stimulation. Finally, taCasp3-mediated ablation of VP\n                  <jats:sup>GABA<\/jats:sup>\n                  neurons reduced intake of palatable liquids and blocked high-fat diet-induced obesity without impacting homeostatic feeding. Together, these findings establish VP\n                  <jats:sup>GABA<\/jats:sup>\n                  neurons as a neural population that preferentially controls hedonic over homeostatic feeding and can be leveraged to block obesity in mice.\n                <\/jats:p>","DOI":"10.64898\/2026.06.18.733195","type":"posted-content","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T22:40:19Z","timestamp":1782254419000},"source":"Crossref","is-referenced-by-count":0,"title":["Ventral pallidal GABAergic neurons control hedonic feeding and obesity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4730-627X","authenticated-orcid":false,"given":"Justin G.","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Washington University in St. Louis, St. Louis MO, USA"},{"name":"Department of Neuroscience, Washington University in St. Louis, St. Louis MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0919-8634","authenticated-orcid":false,"given":"Chang S.","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Washington University in St. Louis, St. Louis MO, USA"},{"name":"Department of Neuroscience, Washington University in St. Louis, St. Louis MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4678-0601","authenticated-orcid":false,"given":"Chantelle L.","family":"Murrell","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University in St. Louis, St. Louis MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2941-4859","authenticated-orcid":false,"given":"Mason R.","family":"Barrett","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University in St. Louis, St. Louis MO, USA"},{"name":"Department of Anesthesiology, Washington University in St. Louis, St. Louis MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2918-7895","authenticated-orcid":false,"given":"Gargi C.","family":"Basu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Washington University in St. Louis, St. Louis MO, USA"},{"name":"Department of Anesthesiology, Washington University in St. Louis, St. Louis MO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5742-0864","authenticated-orcid":false,"given":"Lisa Z.","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Washington University in St. Louis, St. Louis MO, 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