| First Author | Warlow SM | Year | 2024 |
| Journal | Neuron | Volume | 112 |
| Issue | 3 | Pages | 488-499.e5 |
| PubMed ID | 38086374 | Mgi Jnum | J:348666 |
| Mgi Id | MGI:7578723 | Doi | 10.1016/j.neuron.2023.11.002 |
| Citation | Warlow SM, et al. (2023) Mesoaccumbal glutamate neurons drive reward via glutamate release but aversion via dopamine co-release. Neuron |
| abstractText | 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. |
