{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T20:07:33Z","timestamp":1789157253986,"version":"build-2803163510"},"posted":{"date-parts":[[2026,9,8]]},"group-title":"Neuroscience","reference-count":64,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["MH132052"],"award-info":[{"award-number":["MH132052"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30DA013429"],"award-info":[{"award-number":["P30DA013429"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["T32DA007237"],"award-info":[{"award-number":["T32DA007237"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03a63f080","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,8]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>Palatability and metabolic state strongly shape food consumption, making it important to understand the neural mechanisms that integrate these influences. Glucagon-like peptide-1 (GLP-1) receptor agonists are potent modulators of food intake and increasingly used therapeutic options, yet the circuit mechanisms underlying their effects remain unclear. Dorsal striatal inhibitory circuits contribute to reward-guided behavior and feeding, but how they encode ongoing consumption or are altered by GLP-1 receptor agonism is unknown. Using fiber photometry in mice, we found that dorsomedial striatal (DMS) GABA signals decreased at consumption onset, scaled with palatability, predicted licking, and were enhanced by food deprivation. GLP-1 receptor agonist semaglutide reduced intake, disrupted coupling between DMS GABA and licking, enhanced rebound signals preceding pauses, and increased DMS ensemble synchrony. Optogenetic excitation of DMS GABAergic interneurons reproduced key semaglutide-induced changes in consumption structure. These findings suggest that DMS GABA dynamics, as a state-dependent regulator of palatable consumption, are reshaped by GLP-1 receptor agonism.<\/jats:p>","DOI":"10.64898\/2026.09.03.749293","type":"posted-content","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T01:20:16Z","timestamp":1788916816000},"source":"Crossref","is-referenced-by-count":0,"title":["Dorsomedial striatal GABA dynamics organize palatable reward consumption and are reshaped by GLP-1 receptor agonism"],"prefix":"10.64898","author":[{"given":"Aryanna Nichelle","family":"Copling","sequence":"first","affiliation":[{"name":"Center for Substance Abuse Research (CSAR), Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA"},{"name":"Biomedical Sciences Graduate Program, Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oyku","family":"Dinckol","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research (CSAR), Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA"},{"name":"Department of Physiology and Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah Harris","family":"Wenger","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research (CSAR), Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhumiben Pradipkumar","family":"Patel","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research (CSAR), Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezechiel Muanza","family":"N\u2019Kongolo Lukusa","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research (CSAR), Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2700-977X","authenticated-orcid":false,"given":"Munir Gunes","family":"Kutlu","sequence":"additional","affiliation":[{"name":"Center for Substance Abuse Research (CSAR), Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA"},{"name":"Department of Neural Sciences, Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026091112151364000_2026.09.03.749293v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2011.09.004"},{"key":"2026091112151364000_2026.09.03.749293v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3745"},{"key":"2026091112151364000_2026.09.03.749293v1.3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2338-16.2016"},{"key":"2026091112151364000_2026.09.03.749293v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-019-0189-2"},{"key":"2026091112151364000_2026.09.03.749293v1.5","first-page":"167","article-title":"Striatal mechanisms underlying movement, reinforcement, and punishment","volume":"27","year":"2012","journal-title":"Physiol. Bethesda Md"},{"key":"2026091112151364000_2026.09.03.749293v1.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1554-07.2007"},{"key":"2026091112151364000_2026.09.03.749293v1.7","doi-asserted-by":"publisher","DOI":"10.3389\/fncom.2014.00152"},{"key":"2026091112151364000_2026.09.03.749293v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.09.019"},{"key":"2026091112151364000_2026.09.03.749293v1.9","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.55729"},{"key":"2026091112151364000_2026.09.03.749293v1.10","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5097-08.2009"},{"key":"2026091112151364000_2026.09.03.749293v1.11","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.neuron.2016.09.007","article-title":"Principles of Synaptic Organization of GABAergic Interneurons in the Striatum","volume":"92","year":"2016","journal-title":"Neuron"},{"key":"2026091112151364000_2026.09.03.749293v1.12","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4870-09.2010"},{"key":"2026091112151364000_2026.09.03.749293v1.13","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5027-04.2005"},{"key":"2026091112151364000_2026.09.03.749293v1.14","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.neuron.2019.04.016","article-title":"Striatal Low-Threshold Spiking Interneurons Regulate Goal-Directed Learning","volume":"103","year":"2019","journal-title":"Neuron"},{"key":"2026091112151364000_2026.09.03.749293v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2011.04.004"},{"key":"2026091112151364000_2026.09.03.749293v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.01.023"},{"key":"2026091112151364000_2026.09.03.749293v1.17","first-page":"723","article-title":"The early excitatory action of striatal cholinergic-GABAergic microcircuits conditions the subsequent GABA inhibitory shift. Commun","volume":"6","year":"2023","journal-title":"Biol"},{"key":"2026091112151364000_2026.09.03.749293v1.18","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5493-07.2008"},{"key":"2026091112151364000_2026.09.03.749293v1.19","first-page":"3","volume-title":"Handbook of Behavioral Neuroscience","volume":"24","year":"2016"},{"key":"2026091112151364000_2026.09.03.749293v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.04.024"},{"key":"2026091112151364000_2026.09.03.749293v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-00772-7"},{"key":"2026091112151364000_2026.09.03.749293v1.22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2408505121"},{"key":"2026091112151364000_2026.09.03.749293v1.23","doi-asserted-by":"crossref","first-page":"e2313058120","DOI":"10.1073\/pnas.2313058120","article-title":"The roles of surround inhibition for the intrinsic function of the striatum, analyzed in silico","volume":"120","year":"2023","journal-title":"Proc. Natl. Acad. Sci"},{"key":"2026091112151364000_2026.09.03.749293v1.24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2010.07153.x"},{"key":"2026091112151364000_2026.09.03.749293v1.25","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/npp.2009.131","article-title":"Human and rodent homologies in action control: corticostriatal determinants of goal-directed and habitual action","volume":"35","year":"2010","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol"},{"key":"2026091112151364000_2026.09.03.749293v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1919"},{"key":"2026091112151364000_2026.09.03.749293v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.11.005"},{"key":"2026091112151364000_2026.09.03.749293v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2008.12.014"},{"key":"2026091112151364000_2026.09.03.749293v1.29","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00265"},{"key":"2026091112151364000_2026.09.03.749293v1.30","doi-asserted-by":"crossref","first-page":"104726","DOI":"10.1016\/j.neubiorev.2022.104726","article-title":"Role of the striatal dopamine, GABA and opioid systems in mediating feeding and fat intake","volume":"139","year":"2022","journal-title":"Neurosci. Biobehav. Rev"},{"key":"2026091112151364000_2026.09.03.749293v1.31","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00034.2006"},{"key":"2026091112151364000_2026.09.03.749293v1.32","doi-asserted-by":"publisher","DOI":"10.1210\/en.2011-1443"},{"key":"2026091112151364000_2026.09.03.749293v1.33","doi-asserted-by":"crossref","unstructured":"Skibicka, K. P . The central GLP-1: implications for food and drug reward. Front. Neurosci. 7, (2013).","DOI":"10.3389\/fnins.2013.00181"},{"key":"2026091112151364000_2026.09.03.749293v1.34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6326-11.2012"},{"key":"2026091112151364000_2026.09.03.749293v1.35","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12932"},{"key":"2026091112151364000_2026.09.03.749293v1.36","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3262-11.2011"},{"key":"2026091112151364000_2026.09.03.749293v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.362"},{"key":"2026091112151364000_2026.09.03.749293v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEURON.2021.03.011"},{"key":"2026091112151364000_2026.09.03.749293v1.39","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1037\/bne0000216","article-title":"The dorsomedial striatum mediates Pavlovian appetitive conditioning and food consumption","volume":"131","year":"2017","journal-title":"Behav. Neurosci"},{"key":"2026091112151364000_2026.09.03.749293v1.40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3707-13.2014"},{"key":"2026091112151364000_2026.09.03.749293v1.41","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2012.08.014"},{"key":"2026091112151364000_2026.09.03.749293v1.42","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2693-17.2018"},{"key":"2026091112151364000_2026.09.03.749293v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3377"},{"key":"2026091112151364000_2026.09.03.749293v1.44","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2005.04218.x"},{"key":"2026091112151364000_2026.09.03.749293v1.45","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.112.3.678"},{"key":"2026091112151364000_2026.09.03.749293v1.46","doi-asserted-by":"crossref","first-page":"R97","DOI":"10.1152\/ajpregu.1993.264.1.R97","article-title":"Food deprivation-and palatability-induced microstructural changes in ingestive behavior","volume":"264","year":"1993","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol"},{"key":"2026091112151364000_2026.09.03.749293v1.47","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-11-04434.1997"},{"key":"2026091112151364000_2026.09.03.749293v1.48","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.pbb.2010.05.028","article-title":"Intra-accumbens baclofen, but not muscimol, mimics the effects of food withdrawal on feeding behaviour","volume":"97","year":"2010","journal-title":"Pharmacol. Biochem. Behav"},{"key":"2026091112151364000_2026.09.03.749293v1.49","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0115-14.2014"},{"key":"2026091112151364000_2026.09.03.749293v1.50","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.cobeha.2016.02.005","article-title":"GLP-1 influences food and drug reward","volume":"9","year":"2016","journal-title":"Curr. Opin. Behav. Sci"},{"key":"2026091112151364000_2026.09.03.749293v1.51","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1038\/s41586-026-10444-4","article-title":"A brain reward circuit inhibited by next-generation weight-loss drugs in mice","volume":"654","year":"2026","journal-title":"Nature"},{"key":"2026091112151364000_2026.09.03.749293v1.52","doi-asserted-by":"crossref","first-page":"4394","DOI":"10.1038\/s41380-020-00957-3","article-title":"GLP-1 receptor signaling in the laterodorsal tegmental nucleus attenuates cocaine seeking by activating GABAergic circuits that project to the VTA","volume":"26","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"2026091112151364000_2026.09.03.749293v1.53","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adr5051"},{"key":"2026091112151364000_2026.09.03.749293v1.54","doi-asserted-by":"publisher","DOI":"10.1002\/cne.24905"},{"key":"2026091112151364000_2026.09.03.749293v1.55","doi-asserted-by":"crossref","unstructured":"Sandoval-Rodr\u00edguez, R. et al. D1 and D2 neurons in the nucleus accumbens enable positive and negative control over sugar intake in mice. Cell Rep. 42, (2023).","DOI":"10.1016\/j.celrep.2023.112190"},{"key":"2026091112151364000_2026.09.03.749293v1.56","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160575"},{"key":"2026091112151364000_2026.09.03.749293v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.08.037"},{"key":"2026091112151364000_2026.09.03.749293v1.58","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2032183"},{"key":"2026091112151364000_2026.09.03.749293v1.59","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1001\/jamapsychiatry.2024.4789","article-title":"Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial","volume":"82","year":"2025","journal-title":"JAMA Psychiatry"},{"key":"2026091112151364000_2026.09.03.749293v1.60","doi-asserted-by":"crossref","first-page":"RP108319","DOI":"10.7554\/eLife.108319","article-title":"iGABASnFR2 is an improved genetically encoded protein sensor of GABA","volume":"14","year":"2026","journal-title":"eLife"},{"key":"2026091112151364000_2026.09.03.749293v1.61","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2836"},{"key":"2026091112151364000_2026.09.03.749293v1.62","doi-asserted-by":"publisher","DOI":"10.1037\/bne0000029"},{"key":"2026091112151364000_2026.09.03.749293v1.63","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2021.08.052"},{"key":"2026091112151364000_2026.09.03.749293v1.64","doi-asserted-by":"publisher","DOI":"10.64898\/2025.12.10.693585"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.03.749293","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:15:20Z","timestamp":1789154120000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.03.749293"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":64,"URL":"https:\/\/doi.org\/10.64898\/2026.09.03.749293","relation":{},"subject":[],"published":{"date-parts":[[2026,9,8]]},"subtype":"preprint"}}