GABA is localized in dopaminergic synaptic vesicles in the rodent striatum
Abstract
Recently, electrophysiological evidence was given for inhibitory postsynaptic responses at dopaminergic striatal synapses. These responses were independent of the vesicular GABA transporter, VGAT, but dependent on the vesicular dopamine transporter VMAT2. The identity and the exact source of the released molecule, as well as the presence of the putative inhibitory transmitter in VMAT2 containing synaptic vesicles remain to be shown. To clarify this, in particular to determine whether GABA is responsible for the inhibitory response at dopaminergic synapses, we used the electron microscopic immunogold method to label in vivo perfusion fixed striatal tissue with antibodies recognising GABA, VGAT, VMAT2 and tyrosine hydroxylase. We show that about 13 % of tyrosine hydroxylase positive and 11 % of VMAT2 axonal terminals in the caudo-putamen contain significant labelling for GABA. Immunogold signals for tyrosine hydroxylase and VGAT was totally segregated into different pools of nerve terminals. Quantitative analyses of the distance between gold particles signalling GABA and synaptic vesicles showed that GABA was as closely associated with synaptic vesicles in tyrosine hydroxylase positive as in tyrosine hydroxylase negative nerve terminals. Likewise, in dopaminergic terminals GABA and VMAT2 immunogold particles showed a close spatial localization, strongly suggesting the presence of GABA in VMAT2 positive synaptic vesicles. Our results suggest that GABA is exocytosed together with dopamine from dopaminergic nerve terminals in the caudo-putamen through VGAT negative and VMAT2 positive synaptic vesicles.
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Vesicular monoamine transporters can transport GABA into synaptic vesicles.
“It has been reported that vesicular monoamine transporters (Slc8a1 for Vmat1; Slc8a2 for Vmat2) can transport GABA into synaptic vesicles (Stensrud et al., 2014), and virtually all serotonin neurons expressed Vmat2 (Figure 1—figure supplement 1D; Figure 4A left).”
From Single-cell transcriptomes and whole-brain projections of serotonin neurons in the mouse dorsal and median raphe nuclei (2019) · cites this paper as Stensrud et al., 2014
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- Authors
- Stensrud, M. J., Puchades, M., & Gundersen, V.
- Affiliations
- University of Oslo (NO)
- Oslo University Hospital (NO)
- Corresponding author
- Gundersen, Vidar
- Venue
- Brain Structure and Function
- Published
- 2013-07-14
- Volume
- 219
- Issue
- 6
- Pages
- 1901-1912
- ISSN
- 1863-2653 (ISSN-L)
- 1863-2661
- OpenAlex
- W1974369886
- Cited by
- 22
- References
- 64
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 2 · 2019: 2 · 2016: 3 · 2015: 4 · 2014: 2
- FWCI
- 1.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Brain Structure and Function (publishedVersion)
- PubMed (publishedVersion)
- 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 › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- GABA, vesicular monoamine transporter 2, vesicular GABA transporter, tyrosine hydroxylase, caudate-putamen, striatum
- MeSH terms
- Animals, gamma-Aminobutyric Acid, Male, Mice, Inbred C57BL, Synaptic Vesicles, Tyrosine 3-Monooxygenase, Neostriatum, Rats, Wistar, Vesicular Monoamine Transport Proteins, Vesicular Inhibitory Amino Acid Transport Proteins, Dopaminergic Neurons
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