Department of Psychiatry, University of British Columbia at Vancouver Vancouver, BC, Canada.
Front Neurosci. 2013 Apr 10;7:54. doi: 10.3389/fnins.2013.00054. eCollection 2013.
To better understand the connectivity of the brain, it is important to map both structural and functional connections between neurons and cortical regions. In recent years, a set of optogenetic tools have been developed that permit selective manipulation and investigation of neural systems. These tools have enabled the mapping of functional connections between stimulated cortical targets and other brain regions. Advantages of the approach include the ability to arbitrarily stimulate brain regions that express opsins, allowing for brain mapping independent of behavior or sensory processing. The ability of opsins to be rapidly and locally activated allows for investigation of connectivity with spatial resolution on the order of single neurons and temporal resolution on the order of milliseconds. Optogenetic methods for functional mapping have been applied in experiments ranging from in vitro investigation of microcircuits, to in vivo probing of inter-regional cortical connections, to examination of global connections within the whole brain. We review recently developed functional mapping methods that use optogenetic single-point stimulation in the rodent brain and employ cellular electrophysiology, evoked motor movements, voltage sensitive dyes (VSDs), calcium indicators, or functional magnetic resonance imaging (fMRI) to assess activity. In particular we highlight results using red-shifted organic VSDs that permit high temporal resolution imaging in a manner spectrally separated from Channelrhodopsin-2 (ChR2) activation. VSD maps stimulated by ChR2 were dependent on intracortical synaptic activity and were able to reflect circuits used for sensory processing. Although the methods reviewed are powerful, challenges remain with respect to finding approaches that permit selective high temporal resolution assessment of stimulated activity in animals that can be followed longitudinally.
为了更好地理解大脑的连接，绘制神经元和皮质区域之间的结构和功能连接非常重要。近年来，已经开发出了一套光遗传学工具，可以选择性地操作和研究神经系统。这些工具使我们能够绘制受刺激皮质靶标与其他大脑区域之间的功能连接。该方法的优点包括能够任意刺激表达 opsin 的脑区，从而可以进行独立于行为或感觉处理的脑映射。Opsin 能够快速和局部激活的能力允许以单细胞的空间分辨率和毫秒级的时间分辨率来研究连接性。光遗传学功能映射方法已应用于各种实验中，从体外研究微电路，到体内探测皮质区域之间的连接，再到检查整个大脑的全局连接。我们回顾了最近开发的功能映射方法，这些方法在啮齿动物大脑中使用光遗传学单点刺激，并采用细胞电生理学、诱发运动运动、电压敏感染料（VSD）、钙指示剂或功能磁共振成像（fMRI）来评估活性。特别是，我们强调了使用红移有机 VSD 的结果，该方法以与 Channelrhodopsin-2（ChR2）激活光谱分离的方式实现了高时间分辨率成像。由 ChR2 刺激的 VSD 图谱依赖于皮质内突触活动，并且能够反映用于感觉处理的回路。尽管所回顾的方法非常强大，但在寻找允许对可以进行纵向跟踪的动物的刺激活动进行选择性高时间分辨率评估的方法方面仍然存在挑战。
