Mind control with optogenetic mice: Exploring the causal relationships between brain activity and the mind

Every scientific endeavor starts with observation. However, observation alone can only lead to an analysis of correlations. Experimental perturbations are required to understand the causal relationships between the components that constitute the system under study. Our current understanding of the function of the brain, which is a complex multicellular organ, suggests that communication between cells underlies the formation of the mind. This has been mainly deduced from studies of correlations between cell activity and animal behavior. Recently developed tools have enabled the specific control of cell activity. For example, light-sensitive proteins, such as channelrhodopsin-2, that are found in microorganisms can now be genetically expressed in mammalian brain cells, allowing experimenters to optically control cell activity at will. In this review, I introduce the recently established method, Knockin-mediated ENhanced Gene Expression by the improved tetracycline-controlled gene induction (KENGE-tet) method, which has generated a repertoire of transgenic mice that express levels of the highly light-sensitive channelrhodopsin-2 mutant that are sufficient to stimulate multiple cell types. In addition to neurons, manipulations of the activities of nonexcitable glial cells in vivo have also proved possible. A recent report that used the KENGE-tet has shown that the selective optogenetic stimulation of glia can lead to the release of glutamate as a gliotransmitter, synaptic plasticity, and the acceleration of cerebellar-modulated motor learning. These findings have suggested that glia also participate in brain information processing, a function once thought to be solely mediated by neuronal activity. These reports have demonstrated the use of optogenetic tools in exploring the causal relationships between brain activity and the mind.