The development of tools for in vivo mouse brain circuits with optogenetics

Abstract

Methods for the temporally precise control of neuronal activities is one of the most important tools in system neuroscience. Early in 21century, a stable and safety expression model of light sensitive ion channels in mammalian neurons was reported. This microbial opsin could be used to cause or inhibit the electric activities by optical stimulations reliably. This technique was named ‘optogenetics’. With advantage of spatiotemporal precision and cell specificities of optogenetics, many papers have been published, and provide an insight into the functions of the nervous systems. However, the development and convergence of optogenetics, was limited for brain-wide, cell-specific, state-dependent approaches in diverse situations. To overcome the limitation of optogenetics, we needed a multi-modal method for a large scale neuroimaging, so that the electroencephalogram (EEG) can be partial solution of them. EEG is the noninvasive electrophysiological method for recording electrical activities of the brain. EEG has an advantage with its temporally precision, economic feasibility and easiness to use. Because of these advantages, EEG has become a popular and standard method for monitoring brain states in humans. To our knowledge, different frequency bands are classified as different cognitive functions and correlated to a different dynamical structure and a mechanism. In addition, many features of correlation behaviors and functions are thought to be preserved across species, independent of the size of the brain and nervous systems. Our assumption is that information are modulated form with the frequency. Therefore, we stimulate the mouse brain with various frequencies and observe the relation between the stimulus frequency and the observed behavior. In this thesis, we optimized a source localization method for mouse EEG. By adaptation of the source localization method, we visualized a whole brain scale information transfer and feasibility to directly compare with to the human brain mapping techniques. And we optogenetically stimulate the primary somatosensory cortex (S1) with various frequencies to characterize the frequency dependent neural activities, behaviors and cognitive functions. Our approach builds a bridge between the EEG mapping and optically evoked activity in various brain regions. Also, optogenetics combined with EEG can provide an opportunity for investigations not only in neural circuits, but also on the support for behavioral and cognitive functions.