{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T13:10:19Z","timestamp":1790255419134,"version":"4.1.0"},"posted":{"date-parts":[[2026,9,8]]},"group-title":"Neuroscience","reference-count":61,"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\/4.0\/"}],"funder":[{"award":["5P20GM121310"],"award-info":[{"award-number":["5P20GM121310"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2P20GM103432"],"award-info":[{"award-number":["2P20GM103432"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>High-fat diet consumption is linked to a higher risk of obesity, diabetes, cardiometabolic diseases, psychiatric disorders, and cognitive dysfunction. Energy homeostasis and mood fluctuate throughout the 24-hour day, and perturbations in these rhythms have consequences for brain, body, and behavior. Our recent work demonstrates that layer 2\/3 pyramidal neurons in the prelimbic prefrontal cortex (plPFC), a key region in affective behavior and cognitive function, undergo daily rhythms in their physiological function. In this study, we investigate how a one-week acute high-fat diet (aHFD) alters affective behavior and plPFC function. Further, we used time-of-day as a tool to determine how initiation of a HFD impacts the physiological properties of layer 2\/3 plPFC pyramidal neurons in male and female mice. To explore these phenomena, we implemented the open-field test (OFT) and DeepLabCut to gain dynamic whole-body spatiotemporal resolution in our behavioral analysis. Next, we employed patch-clamp electrophysiology to determine how aHFD alters the intrinsic membrane properties and action potential dynamics of these neurons. Here we show that aHFD produces time-of-day dependent changes in exploratory behavior and physiology of plPFC pyramidal neurons, including altered intrinsic properties, firing profiles, and voltage-dependent membrane conductance in both sexes. These results lay the groundwork to explore the physiological mechanisms by which aHFD impacts plPFC function, affective behavior, and cognition. Overall, this study highlights the importance of understanding how diet impacts neural function before the onset of obesity.<\/jats:p>","DOI":"10.64898\/2026.09.02.748924","type":"posted-content","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T22:00:13Z","timestamp":1788904813000},"source":"Crossref","is-referenced-by-count":0,"title":["Brief high-fat diet exposure temporally reshapes affective behavior and prefrontal cortex function"],"prefix":"10.64898","author":[{"given":"Prince Peter","family":"Wormenor","sequence":"first","affiliation":[{"name":"Department of Zoology & Physiology, University of Wyoming, Laramie, WY 82071, USA"},{"name":"Program in Neuroscience, University of Wyoming, Laramie, WY 82071, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan C.","family":"Cupertino","sequence":"additional","affiliation":[{"name":"Department of Zoology & Physiology, University of Wyoming, Laramie, WY 82071, USA"},{"name":"Program in Neuroscience, University of Wyoming, Laramie, WY 82071, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan K.","family":"Crider","sequence":"additional","affiliation":[{"name":"Department of Zoology & Physiology, University of Wyoming, Laramie, WY 82071, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob E.","family":"Turner","sequence":"additional","affiliation":[{"name":"Department of Zoology & Physiology, University of Wyoming, Laramie, WY 82071, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Whitney J.","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Zoology & Physiology, University of Wyoming, Laramie, WY 82071, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9567-1143","authenticated-orcid":false,"given":"Brandon L.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Zoology & Physiology, University of Wyoming, Laramie, WY 82071, USA"},{"name":"Program in Neuroscience, University of Wyoming, Laramie, WY 82071, USA"},{"name":"Department of Animal Science, University of Wyoming, Laramie, WY 82071, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092405550974000_2026.09.02.748924v2.1","unstructured":"CDC. Obesity is a Common, Serious, and Costly Disease. Centers for Disease Control and Prevention https:\/\/www.cdc.gov\/obesity\/data\/adult.html (2022)."},{"key":"2026092405550974000_2026.09.02.748924v2.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01548-4"},{"key":"2026092405550974000_2026.09.02.748924v2.3","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.3390\/nu12051505","article-title":"Cardio-Metabolic Effects of High-Fat Diets and Their Underlying Mechanisms\u2014A Narrative Review","volume":"12","year":"2020","journal-title":"Nutrients"},{"key":"2026092405550974000_2026.09.02.748924v2.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.02.025"},{"key":"2026092405550974000_2026.09.02.748924v2.5","doi-asserted-by":"crossref","unstructured":"Gainey, S. J. et al. Short-Term High-Fat Diet (HFD) Induced Anxiety-Like Behaviors and Cognitive Impairment Are Improved with Treatment by Glyburide. Front. Behav. Neurosci. 10, (2016).","DOI":"10.3389\/fnbeh.2016.00156"},{"key":"2026092405550974000_2026.09.02.748924v2.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2016.10.002"},{"key":"2026092405550974000_2026.09.02.748924v2.7","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.734158"},{"key":"2026092405550974000_2026.09.02.748924v2.8","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.bbr.2018.10.013","article-title":"Circadian misalignment has differential effects on affective behavior following exposure to controllable or uncontrollable stress","volume":"359","year":"2019","journal-title":"Behav. Brain Res"},{"key":"2026092405550974000_2026.09.02.748924v2.9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018375108"},{"key":"2026092405550974000_2026.09.02.748924v2.10","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-012-0252-0"},{"key":"2026092405550974000_2026.09.02.748924v2.11","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12654"},{"key":"2026092405550974000_2026.09.02.748924v2.12","doi-asserted-by":"publisher","DOI":"10.1038\/nature00965"},{"key":"2026092405550974000_2026.09.02.748924v2.13","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2016.03.1050"},{"key":"2026092405550974000_2026.09.02.748924v2.14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609625104"},{"key":"2026092405550974000_2026.09.02.748924v2.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-018-0088-y"},{"key":"2026092405550974000_2026.09.02.748924v2.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2005.05.007"},{"key":"2026092405550974000_2026.09.02.748924v2.17","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.167"},{"key":"2026092405550974000_2026.09.02.748924v2.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.06.028"},{"key":"2026092405550974000_2026.09.02.748924v2.19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906791106"},{"key":"2026092405550974000_2026.09.02.748924v2.20","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1101\/lm.921708","article-title":"Molecular mechanisms of stress-induced prefrontal cortical impairment: implications for mental illness","volume":"15","year":"2008","journal-title":"Learn. Mem. Cold Spring Harb. N"},{"key":"2026092405550974000_2026.09.02.748924v2.21","doi-asserted-by":"crossref","first-page":"4030","DOI":"10.1007\/s12035-022-02806-6","article-title":"PPAR\u03b3 Dysfunction in the Medial Prefrontal Cortex Mediates High-Fat Diet-Induced Depression","volume":"59","year":"2022","journal-title":"Mol. Neurobiol"},{"key":"2026092405550974000_2026.09.02.748924v2.22","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23391"},{"key":"2026092405550974000_2026.09.02.748924v2.23","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-35898-8"},{"key":"2026092405550974000_2026.09.02.748924v2.24","doi-asserted-by":"crossref","first-page":"zsaf210","DOI":"10.1093\/sleep\/zsaf210","article-title":"Perinatal circadian desynchronization disrupts sleep and prefrontal cortex function in adult offspring","volume":"49","year":"2026","journal-title":"Sleep"},{"key":"2026092405550974000_2026.09.02.748924v2.25","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhaf188"},{"key":"2026092405550974000_2026.09.02.748924v2.26","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s11064-026-04791-x","article-title":"Prefrontal Cortex Dysregulation of Amino Acid-Glucose Homeostasis Links High-Fat and\/or High-Fructose Intake to Cognitive Deficits in Male Mice","volume":"51","year":"2026","journal-title":"Neurochem. Res"},{"key":"2026092405550974000_2026.09.02.748924v2.27","doi-asserted-by":"crossref","first-page":"389","DOI":"10.3390\/brainsci14040389","article-title":"A Four-Week High-Fat Diet Induces Anxiolytic-like Behaviors through Mature BDNF in the mPFC of Mice","volume":"14","year":"2024","journal-title":"Brain Sci"},{"key":"2026092405550974000_2026.09.02.748924v2.28","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0831-23.2023"},{"key":"2026092405550974000_2026.09.02.748924v2.29","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s13668-026-00729-5","article-title":"Neurobiological Consequences of High-Fat High-Sugar Diets on the Mesocorticolimbic System: a Narrative Review","volume":"15","year":"2026","journal-title":"Curr. Nutr. Rep"},{"key":"2026092405550974000_2026.09.02.748924v2.30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48800-2"},{"key":"2026092405550974000_2026.09.02.748924v2.31","doi-asserted-by":"crossref","first-page":"207","DOI":"10.3233\/JAD-2010-091414","article-title":"The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat","volume":"21","year":"2010","journal-title":"J. Alzheimers Dis. JAD"},{"key":"2026092405550974000_2026.09.02.748924v2.32","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2007.44"},{"key":"2026092405550974000_2026.09.02.748924v2.33","doi-asserted-by":"publisher","DOI":"10.3791\/52434"},{"key":"2026092405550974000_2026.09.02.748924v2.34","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0209-y"},{"key":"2026092405550974000_2026.09.02.748924v2.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.04.045"},{"key":"2026092405550974000_2026.09.02.748924v2.36","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(03)01272-X"},{"key":"2026092405550974000_2026.09.02.748924v2.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48792-2"},{"key":"2026092405550974000_2026.09.02.748924v2.38","doi-asserted-by":"publisher","DOI":"10.1145\/584091.584093"},{"key":"2026092405550974000_2026.09.02.748924v2.39","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00373-2"},{"key":"2026092405550974000_2026.09.02.748924v2.40","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.2.723"},{"key":"2026092405550974000_2026.09.02.748924v2.41","doi-asserted-by":"publisher","DOI":"10.3791\/53825"},{"key":"2026092405550974000_2026.09.02.748924v2.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpc.2010.04.018"},{"key":"2026092405550974000_2026.09.02.748924v2.43","first-page":"20150202","article-title":"Principal component analysis: a review and recent developments","volume":"374","year":"2016","journal-title":"Philos. Transact. A Math. Phys. Eng. Sci"},{"key":"2026092405550974000_2026.09.02.748924v2.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2011.01.019"},{"key":"2026092405550974000_2026.09.02.748924v2.45","doi-asserted-by":"publisher","DOI":"10.4324\/9780203771587"},{"key":"2026092405550974000_2026.09.02.748924v2.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2019.04.002"},{"key":"2026092405550974000_2026.09.02.748924v2.47","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291703001697"},{"key":"2026092405550974000_2026.09.02.748924v2.48","unstructured":"Mohanty, P. et al. Metabolic Dysfunction in Psychiatric Disorders: A Narrative Review of Shared Pathways Between Mental Illness and Cardiometabolic Disease. Cureus 18, e111469."},{"key":"2026092405550974000_2026.09.02.748924v2.49","doi-asserted-by":"crossref","first-page":"e20240880","DOI":"10.1590\/0001-3765202420240880","article-title":"Short-term high-fat diet alters behavior, peripheral metabolism, and brain mitochondrial function in Swiss mice","volume":"96","year":"2024","journal-title":"An. Acad. Bras. Ci\u00eanc"},{"key":"2026092405550974000_2026.09.02.748924v2.50","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2024.06.007"},{"key":"2026092405550974000_2026.09.02.748924v2.51","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a039107"},{"key":"2026092405550974000_2026.09.02.748924v2.52","doi-asserted-by":"crossref","first-page":"e16210","DOI":"10.1016\/j.heliyon.2023.e16210","article-title":"Explaining adult obesity, severe obesity, and BMI: Five decades of change","volume":"9","year":"2023","journal-title":"Heliyon"},{"key":"2026092405550974000_2026.09.02.748924v2.53","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/s41598-021-03155-5","article-title":"Influence of diurnal phase on behavioral tests of sensorimotor performance, anxiety, learning and memory in mice","volume":"12","year":"2022","journal-title":"Sci. Rep"},{"key":"2026092405550974000_2026.09.02.748924v2.54","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-018-1776-0"},{"key":"2026092405550974000_2026.09.02.748924v2.55","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg049"},{"key":"2026092405550974000_2026.09.02.748924v2.56","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2650-05.2005"},{"key":"2026092405550974000_2026.09.02.748924v2.57","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00146.2017"},{"key":"2026092405550974000_2026.09.02.748924v2.58","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2000.t01-1-00593.x"},{"key":"2026092405550974000_2026.09.02.748924v2.59","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.14343"},{"key":"2026092405550974000_2026.09.02.748924v2.60","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEURON.2019.11.011"},{"key":"2026092405550974000_2026.09.02.748924v2.61","doi-asserted-by":"crossref","first-page":"1480","DOI":"10.1038\/npp.2016.284","article-title":"Obesity-Induced Structural and Neuronal Plasticity in the Lateral Orbitofrontal Cortex","volume":"42","year":"2017","journal-title":"Neuropsychopharmacol. Off. Publ. Am. Coll. Neuropsychopharmacol"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.09.02.748924","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:55:27Z","timestamp":1790254527000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.09.02.748924"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":61,"URL":"https:\/\/doi.org\/10.64898\/2026.09.02.748924","relation":{},"subject":[],"published":{"date-parts":[[2026,9,8]]},"subtype":"preprint"}}