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An action potential initiation mechanism in distal axons for the control of dopamine release
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Information flow in neurons proceeds by integrating inputs in dendrites, generating action potentials near the soma, and releasing neurotransmitters from nerve terminals in the axon. We found that in the striatum, acetylcholine-releasing neurons induce action potential firing in distal dopamine axons. Spontaneous activity of cholinergic neurons produced dopamine release that extended beyond acetylcholine-signaling domains, and traveling action potentials were readily recorded from dopamine axons in response to cholinergic activation. In freely moving mice, dopamine and acetylcholine covaried with movement direction. Local inhibition of nicotinic acetylcholine receptors impaired dopamine dynamics and affected movement. Our findings uncover an endogenous mechanism for action potential initiation independent of somatodendritic integration and establish that this mechanism segregates the control of dopamine signaling between axons and somata.
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“These axonally induced APs are capable of driving DA release in vitro 61 and have been hypothesized to act as a mechanism for local control of DA release within the striatum.[64][65][66][67][68]”
From Synaptic and circuit functions of multitransmitter neurons in the mammalian brain (2023) · cites this paper as [61]
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Metadata
- Authors
- Liu, C., Cai, X., Ritzau-Jost, A., Kramer, P. F., Li, Y., Khaliq, Z. M., Hallermann, S., & Kaeser, P. S.
- Affiliations
- Harvard University (US)
- Carl-Ludwig-Institute of Physiology, Faculty of Medicine, Leipzig University, Leipzig, Germany.
- National Institutes of Health (US)
- Peking University (CN)
- Leipzig University (DE)
- Corresponding author
- Liu, Changliang
- Kaeser, Pascal S.
- ORCID
- Venue
- Science
- Published
- 2022-03-25
- Volume
- 375
- Issue
- 6587
- Pages
- 1378-1385
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC9081985
- OpenAlex
- W4220904128
- Cited by
- 213
- References
- 45
- Citations by year
- 2026: 25 · 2025: 50 · 2024: 56 · 2023: 60 · 2022: 22
- FWCI
- 20.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (P30NS072030, R01NS103484, R01NS083898, ZIANS003135)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD105351)
- 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 › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- action potential generation, distal axons, dopamine release, acetylcholine, cholinergic neurons, nicotinic acetylcholine receptors, striatum, spontaneous neuronal activity, movement direction, axonal signaling
- MeSH terms
- Acetylcholine, Action Potentials, Animals, Axons, Corpus Striatum, Dopamine, Synaptic Transmission, Receptors, Nicotinic, Mice, Cholinergic Neurons
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