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The pericyte connectome: spatial precision of neurovascular coupling is driven by selective connectivity maps of pericytes and endothelial cells and is disrupted in diabetes.
Cell Discovery ( IF 33.5 ) Pub Date : 2020-06-16 , DOI: 10.1038/s41421-020-0180-0
Tamas Kovacs-Oller 1, 2 , Elena Ivanova 1 , Paola Bianchimano 1 , Botir T Sagdullaev 1, 3
Affiliation  

Functional hyperemia, or the matching of blood flow with activity, directs oxygen and nutrients to regionally firing neurons. The mechanisms responsible for this spatial accuracy remain unclear but are critical for brain function and establish the diagnostic resolution of BOLD-fMRI. Here, we described a mosaic of pericytes, the vasomotor capillary cells in the living retina. We then tested whether this net of pericytes and surrounding neuroglia predicted a connectivity map in response to sensory stimuli. Surprisingly, we found that these connections were not only selective across cell types, but also highly asymmetric spatially. First, pericytes connected predominantly to other neighboring pericytes and endothelial cells, and less to arteriolar smooth muscle cells, and not to surrounding neurons or glia. Second, focal, but not global stimulation evoked a directional vasomotor response by strengthening connections along the feeding vascular branch. This activity required local NO signaling and occurred by means of direct coupling via gap junctions. By contrast, bath application of NO or diabetes, a common microvascular pathology, not only weakened the vascular signaling but also abolished its directionality. We conclude that the exclusivity of neurovascular interactions may thus establish spatial accuracy of blood delivery with the precision of the neuronal receptive field size, and is disrupted early in diabetes.



中文翻译:

周细胞连接组:神经血管耦合的空间精度由周细胞和内皮细胞的选择性连接图驱动,并且在糖尿病中被破坏。

功能性充血,或血流与活动的匹配,将氧气和营养物质引导至局部放电神经元。造成这种空间准确性的机制尚不清楚,但对于大脑功能和建立 BOLD-fMRI 的诊断分辨率至关重要。在这里,我们描述了周细胞的镶嵌,即活体视网膜中的血管舒缩毛细血管细胞。然后我们测试了这个周细胞网络和周围的神经胶质细胞是否预测了响应感觉刺激的连接图。令人惊讶的是,我们发现这些连接不仅在细胞类型之间具有选择性,而且在空间上高度不对称。首先,周细胞主要与其他邻近的周细胞和内皮细胞连接,较少与小动脉平滑肌细胞连接,而不与周围的神经元或神经胶质细胞连接。其次,局部刺激而非整体刺激通过加强沿供给血管分支的连接而引起定向血管舒缩反应。该活性需要局部 NO 信号传导,并通过间隙连接直接耦合发生。相比之下,沐浴应用一氧化氮或糖尿病(一种常见的微血管病理)不仅削弱了血管信号传导,而且消除了其方向性。我们的结论是,神经血管相互作用的排他性可能因此以神经元感受野大小的精度建立血液输送的空间准确性,并且在糖尿病早期被破坏。

更新日期:2020-06-16
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