Aldehyde dehydrogenase 1a1 mediates a GABA synthesis pathway in midbrain dopaminergic neurons
Open accessAbstract
An alternative way of making GABA: Midbrain dopaminergic neurons release both the inhibitory neurotransmitter GABA and dopamine. In the central nervous system, GABA synthesis is usually mediated by two glutamate decarboxylases (GAD65 and GAD67). Kim et al. found that midbrain dopaminergic neurons use a different, evolutionary conserved GABA synthesis pathway that is independent of GAD65 and GAD67. These cells synthesize GABA from putrescine via the enzymes diamine oxidase and aldehyde dehydrogenase 1a1. GABA synthesized by this pathway accounts for approximately 70% of co-released GABA. Science , this issue p. 102
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An evolutionarily conserved GABA synthesis pathway mediated by ALDH1a1 has been identified in the ventral tegmental area.
“Intriguingly, an evolutionarily conserved GABA synthesis pathway mediated by aldehyde dehydrogenase 1a1 (ALDH1a1) has been identified in the ventral tegmental area.161”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [161]
In DANs, vMAT2 is required for packaging GABA into vesicles.
“instead, vMAT2 is required for GABA packaging into vesicles 115,116”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [116]
GAT1 is both necessary and sufficient to sustain GABA release in DANs.
“only the GABA transporter, GAT1, is both necessary and sufficient to sustain GABA release in DANs”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [116]
Reducing GABA cotransmission from DANs by genetic deletion of Aldh1a1 increases ethanol intake and preference in mice.
“reducing GABA cotransmission from DANs by genetic deletion of Aldh1a1 increases ethanol intake and preference in mice”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [116]
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- Authors
- Kim, J.-I., Ganesan, S., Luo, S. X., Wu, Y.-W., Park, E., Huang, E. J., Chen, L., & Ding, J. B.
- Affiliations
- Stanford Medicine (US)
- University of California, San Francisco (US)
- San Francisco VA Medical Center (US)
- Corresponding author
- Ding, Jun B.
- Venue
- Science
- Published
- 2015-10-02
- Volume
- 350
- Issue
- 6256
- Pages
- 102-106
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4725325
- OpenAlex
- W2201272991
- Cited by
- 217
- References
- 50
- Citations by year
- 2026: 15 · 2025: 15 · 2024: 19 · 2023: 22 · 2022: 17 · 2021: 21 · 2020: 28 · 2019: 20 · 2018: 9 · 2017: 23 · 2016: 26 · 2015: 2
- FWCI
- 9.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion)
- Funders
- NIH (NS075136, NS091144, MH086403, MH091193)
- National Institute of Mental Health
- National Institute of Neurological Disorders and Stroke
- Klingenstein Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- ALDH1A1, midbrain dopaminergic neurons, glutamic acid decarboxylase, ethanol, binge drinking, alcohol preference, alcohol consumption, addiction, basal ganglia
- MeSH terms
- Aldehyde Dehydrogenase 1 Family, Ethanol, Aldehyde Dehydrogenase, Animals, Female, gamma-Aminobutyric Acid, Male, Mesencephalon, Reward, Sequence Deletion, Evolution, Molecular, Retinal Dehydrogenase, Mice, Metabolic Networks and Pathways, Gene Knockdown Techniques, Dopaminergic Neurons, Binge Drinking
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