Basic Medicine, Neuroscience

Super-network Brain Physiology

In Search for Our Mind: Pursuit of Optogenetic Approach to Reveal the Role of Neuron-Glia Interactions in Mind Formation



Professor, Ph.D.

*Concurrent Position

Research Theme

  • Glial modulation of synaptic transmission
  • Mechanism of glial release of transmitters
  • Determinant of signal transmission via microenvironment of synapse
Research Keywords:

glia, synaptic transmission, intracellular ionic composition, brain ischemia, epilepsy

Technical Keywords:

optogenetics, electrophysiology, acute brain slice, two-photon imaging, electroencephalogram

Laboratory Introduction

Every scientific endeavor starts with observation. However, observation alone can only lead to analysis of correlation. Experimental perturbation is required to understand the causal relationship between the components that constitute the system under study. The brain is a complex multicellular organ. Our current understanding of its function suggests that communication between these cells underlies the formation of the mind. This is mainly deduced from studies of correlation between cell activity and animal behavior. Recently developed tools enable specific control of cell activity. For example, light-sensitive proteins found in microorganisms, such as channelrhodopsin-2, can now be genetically expressed in mammalian brain cells which allow experimenters to optically control cell activity at will. We have introduced various methods to study communication between neuron-to-neuron, neuron-to-glia, and glia-to-neuron. Our recent report using transgenic mice shows that selective optogenetic stimulation of glia can lead to release of glutamate as gliotransmitter, induce synaptic plasticity, and accelerate cerebellar modulated motor learning. This finding suggests that glia also participates in information processing in the brain, a function once thought to be solely mediated by neuronal activity. These reports demonstrate the use of optogenetic tools for exploring the causal relationship between brain activity and mind.

Figure 1. In vivo optogenetic manipulation of glial activity

Figure 1. In vivo optogenetic manipulation of glial activity

Figure 2. Suppression of ischemic damage by optogenetic glial activity

Figure 2. Suppression of ischemic damage by optogenetic glial activity

Recent Publications

  • Nakamura Y, et al. Nanoscale distribution of presynaptic Ca2+ channels and its impact on vesicular release during development. Neuron 85(1):145-158, 2015
  • Beppu K, et al. Optogenetic countering of glial acidosis suppresses glial glutamate release and ischemic brain damage. Neuron 81(2):314-320, 2014
  • Budisantoso T, et al. Evaluation of glutamate concentration transient in the synaptic cleft of the rat calyx of Held. J Physiol 591(1):219-239, 2013
  • Sasaki T, et al. Application of an optogenetic byway for perturbing neuronal activity via glial photostimulation. PNAS 109(50):20720-20725, 2012
  • Tanaka KF, et al. Expanding the repertoire of optogenetically targeted cells with an enhanced gene expression system. Cell Rep 2(2):397-406, 2012.