{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Warlow SM"],"funding":["BLRD VA","NIDA NIH HHS","NIMH NIH HHS","National Institutes of Health","U.S. Department of Veterans Affairs"],"pagination":["488-499.e5"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10922836"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["112(3)"],"pubmed_abstract":["Ventral tegmental area (VTA) projections to the nucleus accumbens (NAc) drive reward-related motivation. Although dopamine neurons are predominant, a substantial glutamatergic projection is also present, and a subset of these co-release both dopamine and glutamate. Optogenetic stimulation of VTA glutamate neurons not only supports self-stimulation but can also induce avoidance behavior, even in the same assay. Here, we parsed the selective contribution of glutamate or dopamine co-release from VTA glutamate neurons to reinforcement and avoidance. We expressed channelrhodopsin-2 (ChR2) in mouse VTA glutamate neurons in combination with CRISPR-Cas9 to disrupt either the gene encoding vesicular glutamate transporter 2 (VGLUT2) or tyrosine hydroxylase (Th). Selective disruption of VGLUT2 abolished optogenetic self-stimulation but left real-time place avoidance intact, whereas CRISPR-Cas9 deletion of Th preserved self-stimulation but abolished place avoidance. Our results demonstrate that glutamate release from VTA glutamate neurons is positively reinforcing but that dopamine release from VTA glutamate neurons can induce avoidance behavior."],"journal":["Neuron"],"pubmed_title":["Mesoaccumbal glutamate neurons drive reward via glutamate release but aversion via dopamine co-release."],"pmcid":["PMC10922836"],"funding_grant_id":["F32MH122192","I01BX005782","R01DA036612","P30DA048736","R01 DA036612","K99 MH130688","I01 BX005782","F32 MH122192","I01 BX003759","K99MH130688","P30 DA048736"],"pubmed_authors":["Dowlat DS","Singhal SM","Faget L","Hnasko TS","Warlow SM","Zell V","Hunker AC","Zweifel LS","Hollon NG"],"additional_accession":[]},"is_claimable":false,"name":"Mesoaccumbal glutamate neurons drive reward via glutamate release but aversion via dopamine co-release.","description":"Ventral tegmental area (VTA) projections to the nucleus accumbens (NAc) drive reward-related motivation. Although dopamine neurons are predominant, a substantial glutamatergic projection is also present, and a subset of these co-release both dopamine and glutamate. Optogenetic stimulation of VTA glutamate neurons not only supports self-stimulation but can also induce avoidance behavior, even in the same assay. Here, we parsed the selective contribution of glutamate or dopamine co-release from VTA glutamate neurons to reinforcement and avoidance. We expressed channelrhodopsin-2 (ChR2) in mouse VTA glutamate neurons in combination with CRISPR-Cas9 to disrupt either the gene encoding vesicular glutamate transporter 2 (VGLUT2) or tyrosine hydroxylase (Th). Selective disruption of VGLUT2 abolished optogenetic self-stimulation but left real-time place avoidance intact, whereas CRISPR-Cas9 deletion of Th preserved self-stimulation but abolished place avoidance. Our results demonstrate that glutamate release from VTA glutamate neurons is positively reinforcing but that dopamine release from VTA glutamate neurons can induce avoidance behavior.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-05-29T14:46:31.796Z","creation":"2025-04-04T00:52:03.115Z"},"accession":"S-EPMC10922836","cross_references":{"pubmed":["38086374"],"doi":["10.1016/j.neuron.2023.11.002"]}}