Striatal Dopamine Release Is Triggered by Synchronized Activity in Cholinergic Interneurons
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Striatal dopamine plays key roles in our normal and pathological goal-directed actions. To understand dopamine function, much attention has focused on how midbrain dopamine neurons modulate their firing patterns. However, we identify a presynaptic mechanism that triggers dopamine release directly, bypassing activity in dopamine neurons. We paired electrophysiological recordings of striatal channelrhodopsin2-expressing cholinergic interneurons with simultaneous detection of dopamine release at carbon-fiber microelectrodes in striatal slices. We reveal that activation of cholinergic interneurons by light flashes that cause only single action potentials in neurons from a small population triggers dopamine release via activation of nicotinic receptors on dopamine axons. This event overrides ascending activity from dopamine neurons and, furthermore, is reproduced by activating ChR2-expressing thalamostriatal inputs, which synchronize cholinergic interneurons in vivo. These findings indicate that synchronized activity in cholinergic interneurons directly generates striatal dopamine signals whose functions will extend beyond those encoded by dopamine neuron activity.
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Inhomogeneous neuronal release of acetylcholine, glutamate and substance P affects dopamine release, which, together with the heterogeneous striosome-matrix compartments, would result in diverse dopamine release.
“Further, inhomogeneous neuronal release of acetylcholine, glutamate and substance P affects dopamine release159–161, which, together with the heterogeneous striosome-matrix compartments, would result in diverse dopamine release.”
From Dopamine reward prediction-error signalling: A two-component response (2016) · cites this paper as [159]
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- Authors
- Threlfell, S., Lalic, T., Platt, N. J., Jennings, K. A., Deisseroth, K., & Cragg, S. J.
- Affiliations
- University of Oxford (GB)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Cragg, Stephanie J.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 75
- Issue
- 1
- Pages
- 58-64
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2075994330
- Cited by
- 845
- References
- 31
- Citations by year
- 2026: 44 · 2025: 62 · 2024: 62 · 2023: 69 · 2022: 77 · 2021: 64 · 2020: 59 · 2019: 67 · 2018: 58 · 2017: 53 · 2016: 70 · 2015: 48 · 2014: 55 · 2013: 41 · 2012: 15
- FWCI
- 20.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Parkinson's UK (G-0808, J-0901)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- striatal dopamine release, cholinergic interneurons, nicotinic acetylcholine receptors, presynaptic dopamine release, neuronal synchronization, channelrhodopsin-2, dopaminergic neurons, carbon fiber microelectrodes, striatum
- MeSH terms
- Action Potentials, Animals, Corpus Striatum, Dopamine, Electric Stimulation, Interneurons, Mice, Inbred C57BL, Mice, Transgenic, Organ Culture Techniques, Mice, Cholinergic Neurons
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