Dopamine activates astrocytes in prefrontal cortex via α1-adrenergic receptors.
Dopamine activates astrocytes in prefrontal cortex via α1-adrenergic receptors.
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DOI：
10.1016/j.celrep.2022.111426
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发表时间：
2022-09-27
期刊：
影响因子：
8.8
通讯作者：
Poskanzer, Kira E.
中科院分区：
文献类型：
--
作者：
Pittolo, Silvia;Yokoyama, Sae;Willoughby, Drew D.;Taylor, Charlotte R.;Reitman, Michael E.;Tse, Vincent;Wu, Zhaofa;Etchenique, Roberto;Li, Yulong;Poskanzer, Kira E.
前额皮质（PFC）是认知控制的枢纽，多巴胺对其功能有着深远的影响。在其他大脑区域，星形胶质细胞感知不同的神经递质和神经调节剂，进而协调神经活性物质的调节。然而，PFC 星形胶质细胞的基本生理学，包括它们响应哪些神经调节信号以及它们如何促进 PFC 功能，尚不清楚。在这里，我们描述了小鼠 PFC 和初级感觉皮层星形胶质细胞中不同的信号特征，这些信号特征显示出对运动的不同反应。我们发现 PFC 星形胶质细胞表达多巴胺受体，但对 Gs/Gi-cAMP 途径没有反应。相反，PFC 星形胶质细胞中的快速钙信号与多巴胺释放时间锁定，并由离体和体内的 α1 肾上腺素受体介导。此外，我们描述了多巴胺触发的 PFC 星形胶质细胞区域细胞外 ATP 的调节。因此，我们确定星形胶质细胞是 PFC 多巴胺能信号传导的活跃参与者，通过神经调节受体串扰促进 PFC 功能。皮托洛等人。证明神经调节剂多巴胺通过另一种神经调节剂去甲肾上腺素的特异性受体靶向星形胶质细胞（一种脑细胞）。这项研究为多巴胺如何影响非神经元脑细胞提供了基础，并表明神经调节途径之间的串扰发生在体内，可能具有临床意义。
The prefrontal cortex (PFC) is a hub for cognitive control, and dopamine profoundly influences its functions. In other brain regions, astrocytes sense diverse neurotransmitters and neuromodulators and, in turn, orchestrate regulation of neuroactive substances. However, basic physiology of PFC astrocytes, including which neuromodulatory signals they respond to and how they contribute to PFC function, is unclear. Here, we characterize divergent signaling signatures in mouse astrocytes of the PFC and primary sensory cortex, which show differential responsiveness to locomotion. We find that PFC astrocytes express receptors for dopamine but are unresponsive through the Gs/Gi-cAMP pathway. Instead, fast calcium signals in PFC astrocytes are time locked to dopamine release and are mediated by α1-adrenergic receptors both ex vivo and in vivo. Further, we describe dopamine-triggered regulation of extracellular ATP at PFC astrocyte territories. Thus, we identify astrocytes as active players in dopaminergic signaling in the PFC, contributing to PFC function though neuromodulator receptor crosstalk. Pittolo et al. demonstrate that the neuromodulator dopamine targets astrocytes, a type of brain cell, via receptors specific to another neuromodulator—norepinephrine. This study provides groundwork on how dopamine affects non-neuronal brain cells and suggests that crosstalk between neuromodulatory pathways occurs in vivo, with possible clinical implications.
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