Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapses
The ventral tegmental area (VTA) contains projection neurons that release the neurotransmitters dopamine, GABA, and/or glutamate from distal synapses. VTA also contains GABA neurons that synapse locally on to dopamine neurons, synapses widely credited to a population of so-called VTA interneurons. I...
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eLife Sciences Publications Ltd
2025-04-01
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| Online Access: | https://elifesciences.org/articles/100085 |
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| author | Lucie Oriol Melody Chao Grace J Kollman Dina S Dowlat Sarthak M Singhal Thomas Steinkellner Thomas S Hnasko |
| author_facet | Lucie Oriol Melody Chao Grace J Kollman Dina S Dowlat Sarthak M Singhal Thomas Steinkellner Thomas S Hnasko |
| author_sort | Lucie Oriol |
| collection | DOAJ |
| description | The ventral tegmental area (VTA) contains projection neurons that release the neurotransmitters dopamine, GABA, and/or glutamate from distal synapses. VTA also contains GABA neurons that synapse locally on to dopamine neurons, synapses widely credited to a population of so-called VTA interneurons. Interneurons in cortex, striatum, and elsewhere have well-defined morphological features, physiological properties, and molecular markers, but such features have not been clearly described in VTA. Indeed, there is scant evidence that local and distal synapses originate from separate populations of VTA GABA neurons. In this study, we tested whether several markers expressed in non-dopamine VTA neurons are selective markers of interneurons, defined as neurons that synapse locally but not distally. Challenging previous assumptions, we found that VTA neurons genetically defined by expression of parvalbumin, somatostatin, neurotensin, or Mu-opioid receptor project to known VTA targets including nucleus accumbens, ventral pallidum, lateral habenula, and prefrontal cortex. Moreover, we provide evidence that VTA GABA and glutamate projection neurons make functional inhibitory or excitatory synapses locally within VTA. These findings suggest that local collaterals of VTA projection neurons could mediate functions prior attributed to VTA interneurons. This study underscores the need for a refined understanding of VTA connectivity to explain how heterogeneous VTA circuits mediate diverse functions related to reward, motivation, or addiction. |
| format | Article |
| id | doaj-art-8f0ee5d1dd5f49ac9c76607fce954193 |
| institution | OA Journals |
| issn | 2050-084X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | eLife Sciences Publications Ltd |
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| spelling | doaj-art-8f0ee5d1dd5f49ac9c76607fce9541932025-08-20T02:17:33ZengeLife Sciences Publications LtdeLife2050-084X2025-04-011310.7554/eLife.100085Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapsesLucie Oriol0https://orcid.org/0009-0009-2966-0911Melody Chao1Grace J Kollman2Dina S Dowlat3Sarthak M Singhal4Thomas Steinkellner5Thomas S Hnasko6https://orcid.org/0000-0001-6176-8513Department of Neurosciences, University of California, San Diego, San Diego, United StatesDepartment of Neurosciences, University of California, San Diego, San Diego, United StatesDepartment of Neurosciences, University of California, San Diego, San Diego, United StatesDepartment of Neurosciences, University of California, San Diego, San Diego, United StatesDepartment of Neurosciences, University of California, San Diego, San Diego, United StatesInstitute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, AustriaDepartment of Neurosciences, University of California, San Diego, San Diego, United States; Research Service VA San Diego Healthcare System, San Diego, United StatesThe ventral tegmental area (VTA) contains projection neurons that release the neurotransmitters dopamine, GABA, and/or glutamate from distal synapses. VTA also contains GABA neurons that synapse locally on to dopamine neurons, synapses widely credited to a population of so-called VTA interneurons. Interneurons in cortex, striatum, and elsewhere have well-defined morphological features, physiological properties, and molecular markers, but such features have not been clearly described in VTA. Indeed, there is scant evidence that local and distal synapses originate from separate populations of VTA GABA neurons. In this study, we tested whether several markers expressed in non-dopamine VTA neurons are selective markers of interneurons, defined as neurons that synapse locally but not distally. Challenging previous assumptions, we found that VTA neurons genetically defined by expression of parvalbumin, somatostatin, neurotensin, or Mu-opioid receptor project to known VTA targets including nucleus accumbens, ventral pallidum, lateral habenula, and prefrontal cortex. Moreover, we provide evidence that VTA GABA and glutamate projection neurons make functional inhibitory or excitatory synapses locally within VTA. These findings suggest that local collaterals of VTA projection neurons could mediate functions prior attributed to VTA interneurons. This study underscores the need for a refined understanding of VTA connectivity to explain how heterogeneous VTA circuits mediate diverse functions related to reward, motivation, or addiction.https://elifesciences.org/articles/100085VTAventral tegmental areadopamineinterneuronrewardopioids |
| spellingShingle | Lucie Oriol Melody Chao Grace J Kollman Dina S Dowlat Sarthak M Singhal Thomas Steinkellner Thomas S Hnasko Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapses eLife VTA ventral tegmental area dopamine interneuron reward opioids |
| title | Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapses |
| title_full | Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapses |
| title_fullStr | Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapses |
| title_full_unstemmed | Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapses |
| title_short | Ventral tegmental area interneurons revisited: GABA and glutamate projection neurons make local synapses |
| title_sort | ventral tegmental area interneurons revisited gaba and glutamate projection neurons make local synapses |
| topic | VTA ventral tegmental area dopamine interneuron reward opioids |
| url | https://elifesciences.org/articles/100085 |
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