Queensland Brain Institute, The University of Queensland, Brisbane, QLD 4072, Australia.
Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD 4072, Australia.
Proc Natl Acad Sci U S A. 2023 Jan 31;120(5):e2202435120. doi: 10.1073/pnas.2202435120. Epub 2023 Jan 24.
The neural circuit of the brain is organized as a hierarchy of functional units with wide-ranging connections that support information flow and functional connectivity. Studies using MRI indicate a moderate coupling between structural and functional connectivity at the system level. However, how do connections of different directions (feedforward and feedback) and regions with different excitatory and inhibitory (E/I) neurons shape the hemodynamic activity and functional connectivity over the hierarchy are unknown. Here, we used functional MRI to detect optogenetic-evoked and resting-state activities over a somatosensory pathway in the mouse brain in relation to axonal projection and E/I distribution. Using a highly sensitive ultrafast imaging, we identified extensive activation in regions up to the third order of axonal projections following optogenetic excitation of the ventral posteriomedial nucleus of the thalamus. The evoked response and functional connectivity correlated with feedforward projections more than feedback projections and weakened with the hierarchy. The hemodynamic response exhibited regional and hierarchical differences, with slower and more variable responses in high-order areas and bipolar response predominantly in the contralateral cortex. Electrophysiological recordings suggest that these reflect differences in neural activity rather than neurovascular coupling. Importantly, the positive and negative parts of the hemodynamic response correlated with E/I neuronal densities, respectively. Furthermore, resting-state functional connectivity was more associated with E/I distribution, whereas stimulus-evoked effective connectivity followed structural wiring. These findings indicate that the structure-function relationship is projection-, cell-type- and hierarchy-dependent. Hemodynamic transients could reflect E/I activity and the increased complexity of hierarchical processing.
大脑的神经回路组织为具有广泛连接的功能单元层次结构，支持信息流和功能连接。使用 MRI 的研究表明，系统水平上结构连接和功能连接之间存在中等程度的耦合。然而，不同方向（前馈和反馈）的连接以及具有不同兴奋性和抑制性（E/I）神经元的区域如何塑造层次结构上的血液动力学活动和功能连接尚不清楚。在这里，我们使用功能磁共振成像（fMRI）来检测与轴突投射和 E/I 分布相关的小鼠大脑体感通路中的光遗传学诱发和静息状态活动。使用高度敏感的超快成像，我们在丘脑腹后内侧核的光遗传学刺激后，在多达第三级轴突投射的区域中识别出广泛的激活。诱发反应和功能连接与前馈投射的相关性强于反馈投射，并且随着层次结构的增加而减弱。血液动力学反应表现出区域和层次差异，在高阶区域中反应较慢且变化较大，在对侧皮质中主要表现为双极反应。电生理记录表明，这些反映了神经活动的差异，而不是神经血管偶联的差异。重要的是，血液动力学响应的正、负部分分别与 E/I 神经元密度相关。此外，静息状态功能连接与 E/I 分布的相关性更强，而刺激诱发的有效连接则遵循结构布线。这些发现表明，结构-功能关系取决于投射、细胞类型和层次结构。血液动力学瞬变可能反映 E/I 活动和分层处理的复杂性增加。
