An axonal brake on striatal dopamine output by cholinergic interneurons

被引：0

作者：

Zhang, Yan-Feng ^{[1
,2
,3
,8
]}

Luan, Pengwei ^{[4
]}

Qiao, Qinbo ^{[1
,2
,3
]}

He, Yiran ^{[1
,2
,3
]}

Zatka-Haas, Peter ^{[1
]}

Zhang, Guofeng ^{[5
,6
]}

Lin, Michael Z. ^{[2
,6
,7
]}

Lak, Armin ^{[1
]}

Jing, Miao ^{[4
]}

Mann, Edward O. ^{[1
]}

Cragg, Stephanie J. ^{[1
,2
,3
]}

机构：

[1] Univ Oxford, Dept Physiol Anat & Genet, Oxford, England

[2] Aligning Sci Parkinsons Collaborat Res Network, Chevy Chase, MD 20815 USA

[3] Univ Oxford, Oxford Parkinsons Dis Ctr, Oxford, England

[4] Chinese Inst Brain Res, Beijing, Peoples R China

[5] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Neurosurg, Guangzhou, Peoples R China

[6] Stanford Univ, Dept Neurobiol, Stanford, CA USA

[7] Stanford Univ, Dept Bioengn, Stanford, CA USA

[8] Univ Exeter, Dept Clin & Biomed Sci, Exeter, England

来源：

NATURE NEUROSCIENCE | 2025年

基金：

英国医学研究理事会;

关键词：

ACETYLCHOLINE-RECEPTORS; DORSAL STRIATUM; TRANSMISSION; RELEASE; MODULATION; DEPENDENCE; MECHANISM; RESPONSES;

D O I：

10.1038/s41593-025-01906-5

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Depolarization of axons is necessary for somatic action potentials to trigger axonal neurotransmitter release. Here we show that striatal cholinergic interneurons (ChIs) and nicotinic receptors (nAChRs) on mouse dopamine axons interrupt this relationship. After nAChR-mediated depolarization, dopamine release by subsequent depolarization events was suppressed for similar to 100 ms. This suppression was not due to depletion of dopamine or acetylcholine, but to a limited reactivation of dopamine axons after nAChR-mediated depolarization, and is more prominent in dorsal than in ventral striatum. In vivo, nAChRs predominantly depressed dopamine release, as nAChR antagonism in dorsal striatum elevated dopamine detected with optic-fiber photometry of dopamine sensor GRAB(DA2m) and promoted conditioned place preference. Our findings reveal that ChIs acting via nAChRs transiently limit the reactivation of dopamine axons for subsequent action potentials in dopamine neurons and therefore generate a dynamic inverse scaling of dopamine release according to ChI activity.

引用

页码：783 / 794

页数：28

共 49 条

[1]

Schultz W., Dayan P., Montague P.R., A neural substrate of prediction and reward, Science, 275, pp. 1593-1599, (1997)

[2]

Rice M.E., Cragg S.J., Nicotine amplifies reward-related dopamine signals in striatum, Nat. Neurosci, 7, pp. 583-584, (2004)

[3]

Sulzer D., Cragg S.J., Rice M.E., Striatal dopamine neurotransmission: regulation of release and uptake, Basal Ganglia, 6, pp. 123-148, (2016)

[4]

Threlfell S., Et al., Striatal dopamine release is triggered by synchronized activity in cholinergic interneurons, Neuron, 75, pp. 58-64, (2012)

[5]

Cachope R., Et al., Selective activation of cholinergic interneurons enhances accumbal phasic dopamine release: setting the tone for reward processing, Cell Rep, 2, pp. 33-41, (2012)

[6]

Mohebi A., Et al., Dissociable dopamine dynamics for learning and motivation, Nature, 570, pp. 65-70, (2019)

[7]

Liu C., Et al., An action potential initiation mechanism in distal axons for the control of dopamine release, Science, 375, pp. 1378-1385, (2022)

[8]

Krok A.C., Et al., Intrinsic dopamine and acetylcholine dynamics in the striatum of mice, Nature, 621, pp. 543-549, (2023)

[9]

Chantranupong L., Et al., Dopamine and glutamate regulate striatal acetylcholine in decision-making, Nature, 621, pp. 577-585, (2023)

[10]

Azcorra M., Et al., Unique functional responses differentially map onto genetic subtypes of dopamine neurons, Nat. Neurosci, 26, pp. 1762-1774, (2023)

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