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 / 28卷 / 04期

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 47 条

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