Differential pial and penetrating arterial responses examined by optogenetic activation of astrocytes and neurons
Differential pial and penetrating arterial responses examined by optogenetic activation of astrocytes and neurons
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DOI：
10.1177/0271678x211010355
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发表时间：
2021-04-25
影响因子：
6.3
通讯作者：
Masamoto, Kazuto
中科院分区：
文献类型：
--
作者：
Hatakeyama, Nao;Unekawa, Miyuki;Masamoto, Kazuto
多种脑细胞通过传递和调节血管活性信号参与神经血管耦合。本研究旨在利用麻醉小鼠皮层中的光遗传学来探测细胞类型依赖性脑血管（即软脑膜和穿通动脉）反应。实验中使用了两系转基因小鼠，它们在皮层神经元（毒蕈碱乙酰胆碱受体）或星形胶质细胞（Mlc1 阳性）中表达阶跃函数类型的光门控阳离子通道（通道视紫红质-2；ChR2）。表达 ChR2 的星形胶质细胞的光激活导致脑血流量 (CBF) 广泛增加，并延伸到未受刺激的外周。相反，表达 ChR2 的神经元的光激活导致 CBF 相对局部增加。 CBF 反应的空间范围的差异可能是由血管室参与的差异来解释的。脑血管反应的体内成像显示，表达 ChR2 的星形胶质细胞激活导致软脑膜动脉和穿通动脉扩张，而表达 ChR2 的神经元激活主要导致穿通小动脉扩张。药理学研究表明，细胞类型特异性信号传导机制参与光遗传学诱导的脑血管反应。总之，表达 ChR2 的星形胶质细胞和神经元不同地诱发软脑膜和穿透动脉血管舒张。
A variety of brain cells participates in neurovascular coupling by transmitting and modulating vasoactive signals. The present study aimed to probe cell type-dependent cerebrovascular (i.e., pial and penetrating arterial) responses with optogenetics in the cortex of anesthetized mice. Two lines of the transgenic mice expressing a step function type of light-gated cation channel (channelrhodopsine-2; ChR2) in either cortical neurons (muscarinic acetylcholine receptors) or astrocytes (Mlc1-positive) were used in the experiments. Photo-activation of ChR2-expressing astrocytes resulted in a widespread increase in cerebral blood flow (CBF), extending to the nonstimulated periphery. In contrast, photo-activation of ChR2-expressing neurons led to a relatively localized increase in CBF. The differences in the spatial extent of the CBF responses are potentially explained by differences in the involvement of the vascular compartments. In vivo imaging of the cerebrovascular responses revealed that ChR2-expressing astrocyte activation led to the dilation of both pial and penetrating arteries, whereas ChR2-expressing neuron activation predominantly caused dilation of the penetrating arterioles. Pharmacological studies showed that cell type-specific signaling mechanisms participate in the optogenetically induced cerebrovascular responses. In conclusion, pial and penetrating arterial vasodilation were differentially evoked by ChR2-expressing astrocytes and neurons.