Cited by 213Neuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on BehaviorNicotinic Acetylcholine Receptors Study

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An action potential initiation mechanism in distal axons for the control of dopamine release

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Liu, Changliang, Cai, Xintong, Ritzau-Jost, Andreas, Kramer, Paul F., Li, Yulong, Khaliq, Zayd M., Hallermann, Stefan, Kaeser, Pascal S.·2022·Science

DOI 10.1126/science.abn0532PMC PMC9081985

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Abstract

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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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: Liu, Changliang
Cai, Xintong
Ritzau-Jost, Andreas
Kramer, Paul F.
Li, Yulong
Khaliq, Zayd M.
Hallermann, Stefan
Kaeser, Pascal S.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2022-03-25
Volume: 375
Issue: 6587
Pages: 1378-1385
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.abn0532
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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An action potential initiation mechanism in distal axons for the control of dopamine release

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