Neuronal heterogeneity in the ventral tegmental area: Distinct contributions to reward circuitry and motivated behavior
The ventral tegmental area (VTA) is a critical component of brain reward circuitry that influences motivation, learning, and emotional regulation. Although this role was traditionally attributed primarily to VTA dopamine (DA) neurons, recent advances in transcriptomics and intersectional genetics ha...
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Elsevier
2025-03-01
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| Series: | Addiction Neuroscience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772392524000506 |
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| author | N. Dalton Fitzgerald Jeremy J. Day |
| author_facet | N. Dalton Fitzgerald Jeremy J. Day |
| author_sort | N. Dalton Fitzgerald |
| collection | DOAJ |
| description | The ventral tegmental area (VTA) is a critical component of brain reward circuitry that influences motivation, learning, and emotional regulation. Although this role was traditionally attributed primarily to VTA dopamine (DA) neurons, recent advances in transcriptomics and intersectional genetics have revealed significant cell type heterogeneity within the VTA, challenging these established notions. Distinct subtypes of DA neurons can be identified across the VTA and substantia nigra pars compacta (SNc) by characteristics that include gene expression patterns (molecular identity), connectivity motifs (network identity), and patterns of task-linked activity and neurotransmitter release (computational identity). This review aims to synthesize current knowledge of diverse neuronal populations in the VTA, including distinct subtypes of DA, glutamate (GLUT), and GABAergic neurons and combinatorial cells alongside well-characterized markers of these neuronal subclasses. Furthermore, this review highlights known projection targets and the role of diverse VTA cell types in motivated behavior. Finally, we highlight emerging intersectional techniques that enable targeted studies of the vast array of cell types and discuss areas of research important for the future direction of the field. Understanding VTA cell type heterogeneity may yield new insights into the reward system, offering potential avenues for treating substance use disorders and other related conditions. |
| format | Article |
| id | doaj-art-66d22d559e89483fa7738470db24aa50 |
| institution | Kabale University |
| issn | 2772-3925 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Addiction Neuroscience |
| spelling | doaj-art-66d22d559e89483fa7738470db24aa502025-01-29T05:02:42ZengElsevierAddiction Neuroscience2772-39252025-03-0114100191Neuronal heterogeneity in the ventral tegmental area: Distinct contributions to reward circuitry and motivated behaviorN. Dalton Fitzgerald0Jeremy J. Day1Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USACorresponding author at: Department of Neurobiology, 1825 University Blvd, SHEL 910, Birmingham, AL 35294.; Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USAThe ventral tegmental area (VTA) is a critical component of brain reward circuitry that influences motivation, learning, and emotional regulation. Although this role was traditionally attributed primarily to VTA dopamine (DA) neurons, recent advances in transcriptomics and intersectional genetics have revealed significant cell type heterogeneity within the VTA, challenging these established notions. Distinct subtypes of DA neurons can be identified across the VTA and substantia nigra pars compacta (SNc) by characteristics that include gene expression patterns (molecular identity), connectivity motifs (network identity), and patterns of task-linked activity and neurotransmitter release (computational identity). This review aims to synthesize current knowledge of diverse neuronal populations in the VTA, including distinct subtypes of DA, glutamate (GLUT), and GABAergic neurons and combinatorial cells alongside well-characterized markers of these neuronal subclasses. Furthermore, this review highlights known projection targets and the role of diverse VTA cell types in motivated behavior. Finally, we highlight emerging intersectional techniques that enable targeted studies of the vast array of cell types and discuss areas of research important for the future direction of the field. Understanding VTA cell type heterogeneity may yield new insights into the reward system, offering potential avenues for treating substance use disorders and other related conditions.http://www.sciencedirect.com/science/article/pii/S2772392524000506DopamineVentral tegmental areaCo-releaseGlutamateGABASingle nucleus RNA-seq |
| spellingShingle | N. Dalton Fitzgerald Jeremy J. Day Neuronal heterogeneity in the ventral tegmental area: Distinct contributions to reward circuitry and motivated behavior Addiction Neuroscience Dopamine Ventral tegmental area Co-release Glutamate GABA Single nucleus RNA-seq |
| title | Neuronal heterogeneity in the ventral tegmental area: Distinct contributions to reward circuitry and motivated behavior |
| title_full | Neuronal heterogeneity in the ventral tegmental area: Distinct contributions to reward circuitry and motivated behavior |
| title_fullStr | Neuronal heterogeneity in the ventral tegmental area: Distinct contributions to reward circuitry and motivated behavior |
| title_full_unstemmed | Neuronal heterogeneity in the ventral tegmental area: Distinct contributions to reward circuitry and motivated behavior |
| title_short | Neuronal heterogeneity in the ventral tegmental area: Distinct contributions to reward circuitry and motivated behavior |
| title_sort | neuronal heterogeneity in the ventral tegmental area distinct contributions to reward circuitry and motivated behavior |
| topic | Dopamine Ventral tegmental area Co-release Glutamate GABA Single nucleus RNA-seq |
| url | http://www.sciencedirect.com/science/article/pii/S2772392524000506 |
| work_keys_str_mv | AT ndaltonfitzgerald neuronalheterogeneityintheventraltegmentalareadistinctcontributionstorewardcircuitryandmotivatedbehavior AT jeremyjday neuronalheterogeneityintheventraltegmentalareadistinctcontributionstorewardcircuitryandmotivatedbehavior |