Long-term optical imaging of neurovascular coupling in mouse cortex using GCaMP6f and intrinsic hemodynamic signals.
Long-term optical imaging of neurovascular coupling in mouse cortex using GCaMP6f and intrinsic hemodynamic signals.
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DOI：
10.1016/j.neuroimage.2017.09.055
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发表时间：
2018-01-15
期刊：
影响因子：
5.7
通讯作者：
Du C
中科院分区：
文献类型：
--
作者：
Gu X;Chen W;You J;Koretsky AP;Volkow ND;Pan Y;Du C
脑血流动力学是根据神经元活动的变化而调节的，这一过程被称为神经血管耦合（NVC），可被神经精神疾病（如中风、阿尔茨海默病）破坏。因此，人们对高时空分辨率的NVC长期动态成像越来越感兴趣。在这里，通过结合使用遗传编码钙指示器和光学技术，我们开发了一个纵向多模态光学成像平台（MIP），可以在单细胞和单血管分辨率下在小鼠体感皮层相对较大的视场上对NVC进行延时跟踪。具体来说，GCaMP6f被用作神经元活动的标记物，它与MIP一起使我们能够同时测量神经元[Ca2+]i荧光，脑血流速度（CBFv）和血流动力学的变化，纵向超过8周。我们发现，注射病毒一周后可以检测到[Ca2+]i荧光，注射病毒两周后局部微血管和灌注损伤恢复。病毒注射后三周，观察到后爪刺激对神经元和CBFv的最大反应。此外，单神经元响应后爪刺激的激活被一致记录，随后是约2秒延迟扩张的连续微血管。此外，静息状态自发性神经元和血流动力学振荡在整个八周的研究中都可以检测到。我们的研究结果表明，MIP能够在高时空分辨率下纵向研究静息状态和刺激诱发的神经元激活期间神经血管网络的组织和可塑性。
Cerebral hemodynamics is modulated in response to changes in neuronal activity, a process termed neurovascular coupling (NVC), which can be disrupted by neuropsychiatric diseases (e.g., stroke, Alzheimer’s disease). Thus, there is growing interest to image long-term NVC dynamics with high spatiotemporal resolutions. Here, by combining the use of a genetically-encoded calcium indicator with optical techniques, we develop a longitudinal multimodal optical imaging platform (MIP) that enabled time-lapse tracking of NVC over a relatively large field of view in the mouse somatosensory cortex at single cell and single vessel resolutions. Specifically, GCaMP6f was used as marker of neuronal activity, which along with MIP allowed us to simultaneously measure the changes in neuronal [Ca2+]i fluorescence, cerebral blood flow velocity (CBFv) and hemodynamics longitudinally for more than eight weeks. We show that [Ca2+]i fluorescence was detectable one week post viral injection and the damage to local microvasculature and perfusion recovered two weeks after injection. By three weeks post viral injection, maximal neuronal and CBFv responses to hindpaw stimulations were observed. Moreover, single neuronal activation in response to hindpaw stimulation was consistently recorded, followed by ~2 second delayed dilation of contiguous microvessels. Additionally, resting-state spontaneous neuronal and hemodynamic oscillations were detectable throughout the eight weeks of study. Our results demonstrate the capability of MIP for longitudinal investigation of the organization and plasticity of the neurovascular network during resting state and during stimulation-evoked neuronal activation at high spatiotemporal resolutions.
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影响因子：
5.7
作者：
Goloshevsky, Artem G.;Wu, Carolyn W. -H.;Dodd, Stephen J.;Koretsky, Alan P.
通讯作者：
Koretsky, Alan P.
影响因子：
5.7
作者：
Buxton, Richard B.
通讯作者：
Buxton, Richard B.
DOI：
10.1073/pnas.1410800111
发表时间：
2014-10-28
影响因子：
11.1
作者：
Du, Congwu;Volkow, Nora D.;Pan, Yingtian
通讯作者：
Pan, Yingtian
DOI：
10.1093/cercor/bhv054
发表时间：
2015-11
期刊：
Cerebral cortex (New York, N.Y. : 1991)
影响因子：
--
作者：
Enger R;Tang W;Vindedal GF;Jensen V;Johannes Helm P;Sprengel R;Looger LL;Nagelhus EA
通讯作者：
Nagelhus EA
影响因子：
3.8
作者：
Chance, B;Anday, E;Thomas, R
通讯作者：
Thomas, R