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标题：Muscarinic regulation of dopamine and glutamate transmission in the nucleus accumbens
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作者：Jung Hoon Shin ; Martín F. Adrover ; Jürgen Wess 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：26
页码：8124-8129
DOI：10.1073/pnas.1508846112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceIncreases in dopamine (DA) concentration in the nucleus accumbens (NAc) are required for reward seeking, motivation, and motor control. In this article, we describe how release of another neurotransmitter, acetylcholine (ACh), affects DA transmission and concentration in the NAc. Specifically, we observed that activation of muscarinic M2 and M4 ACh receptors depressed, whereas activation of muscarinic M5 ACh receptors potentiated, DA transmission in the NAc. These findings reconcile a long-standing controversy on the roles of muscarinic receptors on DA transmission in the NAc and are highly relevant for the development of novel muscarinic drugs aimed at modulating dopaminergic signaling for therapeutic purposes. Cholinergic transmission in the striatum functions as a key modulator of dopamine (DA) transmission and synaptic plasticity, both of which are required for reward and motor learning. Acetylcholine (ACh) can elicit striatal DA release through activation of nicotinic ACh receptors (nAChRs) on DA axonal projections. However, it remains controversial how muscarinic ACh receptors (mAChRs) modulate striatal DA release, with studies reporting both potentiation and depression of striatal DA transmission by mAChR agonists. This study investigates the mAChR-mediated regulation of release from three types of midbrain neurons that project to striatum: DA, DA/glutamate, and glutamate neurons. We found that M5 mAChRs potentiate DA and glutamate release only from DA and DA/glutamate projections from the midbrain. We also show that M2/M4 mAChRs depress the nAChR-dependent mechanism of DA release in the striatum. These results suggest that M5 receptors on DA neuron terminals enhance DA release, whereas M2/M4 autoreceptors on cholinergic terminals inhibit ACh release and subsequent nAChR-dependent DA release. Our findings clarify the mechanisms of mAChR-dependent modulation of DA and glutamate transmission in the striatum.
关键词：dopamine neurons ; synaptic transmission ; muscarinic receptors ; nicotinic receptors ; dopamine release