Dopamine elevates and lowers astroglial Ca(2+) through distinct pathways depending on local synaptic circuitry.
Dopamine elevates and lowers astroglial Ca(2+) through distinct pathways depending on local synaptic circuitry.
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作者：
Jennings A;Tyurikova O;Bard L;Zheng K;Semyanov A;Henneberger C;Rusakov DA
虽然培养的星形胶质细胞对多巴胺的反应总是伴随着胞浆Ca2+的升高，但星形胶质细胞对多巴胺的敏感性及其生理作用尚不清楚。为了最大限度地减少实验操作对星形胶质生理的影响，在这里，我们监测了通过间隙连接连接到星形胶质细胞的细胞中的Ca2+，这些细胞装载了整个细胞，在急性海马片的CA1区有细胞质指标。针对[Ca2+]测量的高灵敏度，我们还采用了Ca2+指示剂俄勒冈绿BAPTA‐1的终身成像。我们发现多巴胺在辐射层星形胶质细胞中触发了剂量依赖性的双向Ca2+反应，锯齿状升高伴随并随后低于基线的降低。升高依赖于D1/D2受体，并参与细胞内Ca2+的储存和去除，而多巴胺诱导的[Ca2+]减少仅涉及D2受体，并对Ca2+通道阻断敏感。相反，凹层分子星形胶质细胞产生高阈值多巴胺诱导的Ca2+反应，不依赖于多巴胺受体，并且与多巴胺对局部穿孔通路突触的显著抑制作用分离。因此，我们的研究结果表明，一种单一的神经递质——多巴胺——可以根据所涉及的受体来升高或降低星形胶质细胞[Ca2+]，这种作用是特定于区域神经回路的，它们可能与多巴胺在局部突触上的作用不耦合。结果还表明，通常在星形胶质细胞中检测到的[Ca2+]升高可以代表微观尺度上作用的各种不同机制。神经胶质2017;65:447 - 459
Whilst astrocytes in culture invariably respond to dopamine with cytosolic Ca2+ rises, the dopamine sensitivity of astroglia in situ and its physiological roles remain unknown. To minimize effects of experimental manipulations on astroglial physiology, here we monitored Ca2+ in cells connected via gap junctions to astrocytes loaded whole‐cell with cytosolic indicators in area CA1 of acute hippocampal slices. Aiming at high sensitivity of [Ca2+] measurements, we also employed life‐time imaging of the Ca2+ indicator Oregon Green BAPTA‐1. We found that dopamine triggered a dose‐dependent, bidirectional Ca2+ response in stratum radiatum astroglia, a jagged elevation accompanied and followed by below‐baseline decreases. The elevation depended on D1/D2 receptors and engaged intracellular Ca2+ storage and removal whereas the dopamine‐induced [Ca2+] decrease involved D2 receptors only and was sensitive to Ca2+ channel blockade. In contrast, the stratum lacunosum moleculare astroglia generated higher‐threshold dopamine‐induced Ca2+ responses which did not depend on dopamine receptors and were uncoupled from the prominent inhibitory action of dopamine on local perforant path synapses. Our findings thus suggest that a single neurotransmitter—dopamine—could either elevate or decrease astrocyte [Ca2+] depending on the receptors involved, that such actions are specific to the regional neural circuitry and that they may be causally uncoupled from dopamine actions on local synapses. The results also indicate that [Ca2+] elevations commonly detected in astroglia can represent the variety of distinct mechanisms acting on the microscopic scale. GLIA 2017;65:447–459