Dopamine-Evoked Synaptic Regulation in the Nucleus Accumbens Requires Astrocyte Activity
Dopamine-Evoked Synaptic Regulation in the Nucleus Accumbens Requires Astrocyte Activity
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DOI：
10.1016/j.neuron.2019.12.026
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发表时间：
2020-03-18
期刊：
影响因子：
16.2
通讯作者：
Araque, Alfonso
中科院分区：
文献类型：
--
作者：
Corkrum, Michelle;Covelo, Ana;Araque, Alfonso
多巴胺参与学习和记忆，运动控制和奖励等生理过程，以及帕金森病和成瘾等病理状态。与对神经元的广泛研究相反，星形胶质细胞参与多巴胺能信号传导仍然是未知的。利用转基因小鼠、光遗传学和药物遗传学，我们研究了星形胶质细胞对多巴胺能系统的作用。我们发现，在自由行为的小鼠，星形胶质细胞在核的脑桥（NAc），在大脑中的一个关键的奖励中心，响应与Ca 2+升高突触释放的多巴胺，一种现象增强安非他明。在脑切片中，突触释放的多巴胺增加星形胶质细胞Ca 2+，刺激ATP/腺苷的释放，并通过激活突触前A（1）受体抑制兴奋性突触传递。安非他明通过刺激星形胶质细胞和随后的A（1）受体激活来抑制神经传递。此外，星形胶质细胞调节安非他明的急性行为精神影响。因此，星形胶质细胞介导多巴胺和安非他明诱导的突触调节，揭示了大脑奖赏系统中的一种新的细胞通路。
Dopamine is involved in physiological processes like learning and memory, motor control and reward, and pathological conditions such as Parkinson's disease and addiction. In contrast to the extensive studies on neurons, astrocyte involvement in dopaminergic signaling remains largely unknown. Using transgenic mice, optogenetics, and pharmacogenetics, we studied the role of astrocytes on the dopaminergic system. We show that in freely behaving mice, astro-cytes in the nucleus accumbens (NAc), a key reward center in the brain, respond with Ca2+ elevations to synaptically released dopamine, a phenomenon enhanced by amphetamine. In brain slices, synaptically released dopamine increases astrocyte Ca2+, stimulates ATP/adenosine release, and depresses excitatory synaptic transmission through activation of presynaptic A(1) receptors. Amphetamine de-presses neurotransmission through stimulation of astrocytes and the consequent A(1) receptor activation. Furthermore, astrocytes modulate the acute behavioral psychomotor effects of amphetamine. Therefore, astrocytes mediate the dopamine- and amphetamine-induced synaptic regulation, revealing a novel cellular pathway in the brain reward system.