{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:30:16Z","timestamp":1785429016960,"version":"3.56.0"},"posted":{"date-parts":[[2026,2,12]]},"group-title":"Neuroscience","reference-count":50,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T00:00:00Z","timestamp":1770854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["R01 AA027544"],"award-info":[{"award-number":["R01 AA027544"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01 DA034696"],"award-info":[{"award-number":["R01 DA034696"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R25 DA057802"],"award-info":[{"award-number":["R25 DA057802"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F31 DA062412"],"award-info":[{"award-number":["F31 DA062412"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30 DA048742"],"award-info":[{"award-number":["P30 DA048742"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,2,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>Studies employing optogenetic approaches in rodent models have highlighted the important contribution of ventral tegmental area (VTA) dopamine (DA) neurons to reward, learning, and motivation. Selective manipulation of VTA DA neurons is generally achieved in these studies using transgenic mouse or rat lines that express Cre recombinase under the control of a promoter active in DA neurons, combined with intra-VTA infusion of adeno-associated virus (AAV) vectors harboring Cre recombinase-dependent expression cassettes. Reliance on transgenic Cre driver lines is expensive and decreases study efficiency, and available driver lines have unique limitations. Here, we report the development of an AAV-only approach that permits genetic access to VTA DA neurons and can support optogenetic self-stimulation in mice. We used a 2.5 kb fragment of the mouse tyrosine hydroxylase promoter (mTH) to drive Cre expression in VTA DA neurons. Intra-VTA co-infusion of AAV8-mTH-Cre with an AAV vector harboring a Cre-dependent yellow fluorescent protein expression cassette yielded high efficiency (82%) and high fidelity (73%) targeting of tyrosine hydroxylase-positive VTA neurons in C57BL\/6J mice. Co-infusion of AAV8-mTH-Cre with a vector harboring a Cre-dependent channelrhodopsin (ChR2) expression cassette permitted optical regulation of VTA neurons with electrophysiological features consistent with VTA DA neurons. Moreover, C57BL\/6J mice expressing ChR2 in VTA DA neurons rapidly acquired optical self-stimulation behavior. Thus, this AAV-only approach should facilitate investigation of VTA DA neuron contributions to reward-related behaviors and permit comparative assessments in reward circuit function in inbred and mutant mouse strains.<\/jats:p>","DOI":"10.64898\/2026.02.10.705134","type":"posted-content","created":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T20:30:12Z","timestamp":1770928212000},"source":"Crossref","is-referenced-by-count":0,"title":["AAV-only targeting of ventral tegmental area dopamine neurons for optical self-stimulation studies in mice"],"prefix":"10.64898","author":[{"given":"Ezequiel","family":"Marron Fernandez de Velasco","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Minnesota, Minneapolis, MN USA 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"IV","given":"John C.","family":"Brent","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Minnesota, Minneapolis, MN USA 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex L.","family":"Welter","sequence":"additional","affiliation":[{"name":"Molecular Pharmacology and Therapeutics Graduate Program, University of Minnesota, Minneapolis, MN USA 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praseuth","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Minnesota, Minneapolis, MN USA 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annelise","family":"Wickman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Minnesota, Minneapolis, MN USA 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric H.","family":"Mitten","sequence":"additional","affiliation":[{"name":"Graduate Program in Neuroscience, University of Minnesota, Minneapolis, MN USA 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5179-9540","authenticated-orcid":false,"given":"Kevin","family":"Wickman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Minnesota, Minneapolis, MN USA 55455"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026021518101006000_2026.02.10.705134v1.1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0030437"},{"key":"2026021518101006000_2026.02.10.705134v1.2","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/S2215-0366(16)00104-8","article-title":"Neurobiology of addiction: A neurocircuitry analysis","volume":"3","year":"2016","journal-title":"Lancet Psychiatry"},{"key":"2026021518101006000_2026.02.10.705134v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2013.03.019"},{"key":"2026021518101006000_2026.02.10.705134v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2016.32"},{"key":"2026021518101006000_2026.02.10.705134v1.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.adh8287"},{"key":"2026021518101006000_2026.02.10.705134v1.6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-070815-013920"},{"key":"2026021518101006000_2026.02.10.705134v1.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.1168878"},{"key":"2026021518101006000_2026.02.10.705134v1.8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033612"},{"key":"2026021518101006000_2026.02.10.705134v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/nature11740"},{"key":"2026021518101006000_2026.02.10.705134v1.10","first-page":"687469","article-title":"Optogenetic activation of the excitatory neurons expressing CaMKIIalpha in the ventral tegmental area upregulates the locomotor activity of free behaving rats","volume":"2014","year":"2014","journal-title":"Biomed. 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