The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Cholinergic Interneurons Mediate Fast VGluT3-Dependent Glutamatergic Transmission in the Striatum
Open accessAbstract
The neurotransmitter glutamate is released by excitatory projection neurons throughout the brain. However, non-glutamatergic cells, including cholinergic and monoaminergic neurons, express markers that suggest that they are also capable of vesicular glutamate release. Striatal cholinergic interneurons (CINs) express the Type-3 vesicular glutamate transporter (VGluT3), although whether they form functional glutamatergic synapses is unclear. To examine this possibility, we utilized mice expressing Cre-recombinase under control of the endogenous choline acetyltransferase locus and conditionally expressed light-activated Channelrhodopsin2 in CINs. Optical stimulation evoked action potentials in CINs and produced postsynaptic responses in medium spiny neurons that were blocked by glutamate receptor antagonists. CIN-mediated glutamatergic responses exhibited a large contribution of NMDA-type glutamate receptors, distinguishing them from corticostriatal inputs. CIN-mediated glutamatergic responses were insensitive to antagonists of acetylcholine receptors and were not seen in mice lacking VGluT3. Our results indicate that CINs are capable of mediating fast glutamatergic transmission, suggesting a new role for these cells in regulating striatal activity.
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“Glutamate release onto SPNs activates postsynaptic ionotropic glutamate receptors with distinct AMPA/NMDA ratios compared with cortico-striatal synapses, suggesting distinct plasticity rules from these disparate inputs.60”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [60]
In the citing paper
“Striatal cholinergic interneurons (CINs) cotransmit Ach and glutamate locally onto spiny projection neurons (SPNs) 60 and dopaminergic axonal terminals.[61][62][63]”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [60]
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Citations
Cites
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Morris, G., Arkadir, D., Nevet, A., Vaadia, E., & Bergman, H. (2004) · Neuron · doi:10.1016/j.neuron.2004.06.012 · Cited by 574
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Sulzer, D. L., Joyce, M. P., Lin, L., Geldwert, D., Haber, S. N., Hattori, T., & Rayport, S. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-12-04588.1998 · Cited by 304 · cited 1×
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Self-citationCompetitive regulation of synaptic Ca2+ influx by D2 dopamine and A2A adenosine receptors
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“To directly compare optically-evoked glutamatergic inputs from CINs with similarly evoked inputs from cortical afferents, we expressed a Cre recombinase-independent version of the ChR2mCherry fusion protein in motor cortex neurons projecting to the striatum [27].”
BackgroundFast synaptic subcortical control of hippocampal circuits
Varga, V., Losonczy, A., Zemelman, B. V., Borhegyi, Z., Nyiri, G., Domonkos, A., Hangya, B., Holderith, N., Magee, J. C., & Freund, T. F. (2009) · Science · doi:10.1126/science.1178307 · Cited by 248 · cited 2×
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“with tyrosine hydroxylase in brainstem catecholaminergic neurons [4].”
BackgroundDopamine Neurons Mediate a Fast Excitatory Signal via Their Glutamatergic Synapses
Chuhma, N., Zhang, H., Masson, J., Zhuang, X., Sulzer, D. L., Hen, R., & Rayport, S. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.4317-03.2004 · Cited by 228 · cited 2×
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Izzo, P. N., & Bolam, J. P. (1988) · The Journal of Comparative Neurology · doi:10.1002/cne.902690207 · Cited by 213 · cited 1×
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BackgroundThe vesicular glutamate transporter VGLUT3 synergizes striatal acetylcholine tone
Gras, C., Amilhon, B., Lepicard, È. M., Poirel, O., Vinatier, J., Herbin, M., Dumas, S., Tzavara, E. T., Wade, M. R., Nomikos, G. G., et al. (2008) · Nature Neuroscience · doi:10.1038/nn2052 · Cited by 211 · cited 6×
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“This model is consistent with the hypothesis that ACh acts primarily via volume transmission [32].”
ResultManns, I. D., Mainville, L., & Jones, B. E. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00302-5 · Cited by 186 · cited 1×
“enzyme, in cholinergic and dopaminergic neurons [2,3].”
Leading tonically active neurons of the striatum from reward detection to context recognition
Apicella, P. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.03.011 · Cited by 186 · cited 3×
“Conversely, in vivo TANs, which are thought to correspond to cholinergic neurons, transiently reduce their firing in response to behaviorally relevant sensory cues [19], suggesting that appropriately timed pauses in glutamate release may contribute to learning stimulus-reward associations.”
BackgroundInfluentialRecurrent Inhibitory Network among Striatal Cholinergic Interneurons
Sullivan, M. A., Chen, H., & Morikawa, H. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2411-08.2008 · Cited by 142 · cited 1×
“striatal cells, CINs are hypothesized to regulate striatal synaptic transmission and long-term plasticity via nicotinic and muscarinic ACh receptors [20,21,22].”
BackgroundSynaptic glutamate release by postnatal rat serotonergic neurons in microculture
Johnson, M. D. (1994) · Neuron · doi:10.1016/0896-6273(94)90283-6 · Cited by 137
Kaneko, T., Akiyama, H., Nagatsu, I., & Mizuno, N. (1990) · Brain Research · doi:10.1016/0006-8993(90)90535-j · Cited by 126 · cited 1×
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Cholinergic modulation of multivesicular release regulates striatal synaptic potency and integration
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Cited by
Sorted by citations
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“This establishes even broader implications, given that glutamate released from cholinergic interneurons mediates not only excitation of medium spiny neurons, as previously described (Higley et al., 2011), but also shapes accumbal dopamine release.”
InfluentialNeurotransmitter Corelease: Mechanism and Physiological Role
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“Consistent with VGLUT3 expression by these cells, the response was abolished in VGLUT3 KO mice (110).”
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“However, the effect of insulin on evoked [DA] o was absent throughout the striatal complex in forebrain ChAT KO mice, demonstrating that insulin-mediated enhancement of DA release requires striatal ACh, but not co-released transmitters from ChIs, such as glutamate 36 .”
Striatal Local Circuitry: A New Framework for Lateral Inhibition
Burke, D. A., Rotstein, H. G., & Alvarez, V. A. (2017) · Neuron · doi:10.1016/j.neuron.2017.09.019 · Cited by 287
Striatal cholinergic interneuron regulation and circuit effects
Lim, S. A. O., Kang, U. J., & McGehee, D. S. (2014) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2014.00022 · Cited by 244
“Striatal ChIs also co-release glutamate with ACh (Higley et al., 2011).”
Background
Metadata
- Authors
- Higley, M. J., Gittis, A. H., Oldenburg, I. A., Balthasar, N., Seal, R. P., Edwards, R. H., Lowell, B. B., Kreitzer, A. C., & Sabatini, B. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- University of California, San Francisco (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Sabatini, Bernardo L.
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-04-22
- Volume
- 6
- Issue
- 4
- Pages
- e19155
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3081336
- OpenAlex
- W2137833675
- Cited by
- 175
- References
- 35
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 10 · 2022: 14 · 2021: 11 · 2020: 14 · 2019: 10 · 2018: 12 · 2017: 16 · 2016: 14 · 2015: 16 · 2014: 12 · 2013: 10 · 2012: 13
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- KiltHub Repository (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Bristol Research (University of Bristol) (submittedVersion)
- KiltHub Repository (cc-by)
- Funders
- Howard Hughes Medical Institute
- W. M. Keck Foundation
- Parkinson's Disease Foundation
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (DK057521, DK046200, DA10154, NS046579)
- National Institute of Mental Health (F32MH068085, MH50712, R01MH050712, R37MH050712, F31MH093026)
- National Institute on Drug Abuse (P01DA010154, DA-10154)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK057521, R01DK075632, P30DK046200, DK075632)
- National Institute of Neurological Disorders and Stroke (NS064984, R01NS046579, F32NS063663, R01NS064984, R37NS046579, NS063663, NS046579)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Keywords
- cholinergic interneurons, striatum, VGLUT3, glutamatergic neurotransmission, medium spiny neurons, NMDA receptor, choline acetyltransferase, channelrhodopsin-2, optogenetic stimulation
- MeSH terms
- Channelrhodopsins, Central Nervous System Stimulants, Animals, Corpus Striatum, Evoked Potentials, Female, Interneurons, Male, Mecamylamine, Picrotoxin, Receptors, Cholinergic, Scopolamine, Receptors, N-Methyl-D-Aspartate, Amino Acid Transport Systems, Acidic, Mice
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