Stimulation-induced increases in cerebral blood flow and local capillary vasoconstriction depend on conducted vascular responses

Stimulation-induced increases in cerebral blood flow and local capillary vasoconstriction depend on conducted vascular responses
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DOI:
10.1073/pnas.1707702115
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发表时间:
2018-06-19
影响因子:
11.1
通讯作者:
Lauritzen, Martin J.
Lauritzen, Martin J.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Cai, Changsi;Fordsmann, Jonas C.;Lauritzen, Martin J.

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功能性神经影像(例如功能磁共振成像)基于耦合神经元活动以及伴随的脑血流量 (CBF) 和新陈代谢的变化。然而,CBF 与穿通小动脉和毛细血管水平事件之间的关系尚未明确。最近的研究结果表明,毛细血管在 CBF 控制中发挥着积极作用,毛细血管上的周细胞可能是 CBF 的主要调节者和功能成像信号的启动者。在这里,我们使用活体小鼠大脑的双光子显微镜,证明刺激引起的小鼠体感皮层突触活动的增加会引起毛细血管扩张,主要从一级或二级毛细血管开始,以 5-20 μm/s 的速度向上游和下游传播。因此,我们的数据支持周细胞在脑血管控制中的积极作用。通过微量吸管吹气将胶质递质 ATP 施加到一级和二级毛细血管,诱导扩张,然后收缩,也以 5-20 μm/s 的速度传播。 ATP 诱导的毛细血管收缩被嘌呤能 P2 受体阻断。因此,毛细血管中传导的血管反应可能是先前未识别的脑血管功能和功能性神经影像信号的调节剂。
Functional neuroimaging, such as fMRI, is based on coupling neuronal activity and accompanying changes in cerebral blood flow (CBF) and metabolism. However, the relationship between CBF and events at the level of the penetrating arterioles and capillaries is not well established. Recent findings suggest an active role of capillaries in CBF control, and pericytes on capillaries may be major regulators of CBF and initiators of functional imaging signals. Here, using two-photon microscopy of brains in living mice, we demonstrate that stimulation-evoked increases in synaptic activity in the mouse somatosensory cortex evokes capillary dilation starting mostly at the first- or second-order capillary, propagating upstream and downstream at 5-20 mu m/s. Therefore, our data support an active role of pericytes in cerebrovascular control. The gliotransmitter ATP applied to first- and second-order capillaries by micropipette puffing induced dilation, followed by constriction, which also propagated at 5-20 mu m/s. ATP-induced capillary constriction was blocked by purinergic P2 receptors. Thus, conducted vascular responses in capillaries may be a previously unidentified modulator of cerebrovascular function and functional neuroimaging signals.