McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
J Neurophysiol. 2011 Mar;105(3):1393-405. doi: 10.1152/jn.00828.2010. Epub 2010 Dec 15.
Behaviors and brain disorders involve neural circuits that are widely distributed in the brain. The ability to map the functional connectivity of distributed circuits, and to assess how this connectivity evolves over time, will be facilitated by methods for characterizing the network impact of activating a specific subcircuit, cell type, or projection pathway. We describe here an approach using high-resolution blood oxygenation level-dependent (BOLD) functional MRI (fMRI) of the awake mouse brain-to measure the distributed BOLD response evoked by optical activation of a local, defined cell class expressing the light-gated ion channel channelrhodopsin-2 (ChR2). The utility of this opto-fMRI approach was explored by identifying known cortical and subcortical targets of pyramidal cells of the primary somatosensory cortex (SI) and by analyzing how the set of regions recruited by optogenetically driven SI activity differs between the awake and anesthetized states. Results showed positive BOLD responses in a distributed network that included secondary somatosensory cortex (SII), primary motor cortex (MI), caudoputamen (CP), and contralateral SI (c-SI). Measures in awake compared with anesthetized mice (0.7% isoflurane) showed significantly increased BOLD response in the local region (SI) and indirectly stimulated regions (SII, MI, CP, and c-SI), as well as increased BOLD signal temporal correlations between pairs of regions. These collective results suggest opto-fMRI can provide a controlled means for characterizing the distributed network downstream of a defined cell class in the awake brain. Opto-fMRI may find use in examining causal links between defined circuit elements in diverse behaviors and pathologies.
行为和大脑障碍涉及广泛分布在大脑中的神经回路。通过描述激活特定亚回路、细胞类型或投射途径对网络影响的方法，将有助于绘制分布式电路的功能连接图，并评估这种连接如何随时间演变。在这里，我们描述了一种使用清醒小鼠大脑高分辨率血氧水平依赖（BOLD）功能磁共振成像（fMRI）的方法-测量光激活表达光门控离子通道通道视紫红质-2（ChR2）的局部、定义的细胞类别的光学激活所诱发的分布式 BOLD 反应。通过鉴定初级体感皮层（SI）锥体神经元的已知皮层和皮层下靶标，并分析光遗传驱动的 SI 活性募集的区域集在清醒和麻醉状态下的差异，探索了这种光 fMRI 方法的实用性。结果显示，在一个包括次级体感皮层（SII）、初级运动皮层（MI）、尾壳核（CP）和对侧 SI（c-SI）的分布式网络中出现阳性 BOLD 反应。与麻醉小鼠（0.7%异氟烷）相比，清醒小鼠的测量结果显示，局部区域（SI）和间接刺激区域（SII、MI、CP 和 c-SI）的 BOLD 反应显著增加，并且 BOLD 信号之间的时间相关性增加了区域对。这些综合结果表明，光 fMRI 可以为在清醒大脑中定义的细胞类别的下游的分布式网络提供一种受控的特征描述方法。光 fMRI 可能在检查不同行为和病理学中定义的电路元件之间的因果关系方面找到用途。
