The structure and function of brain circuits are finely controlled in space and time to generate diverse brain
functions. Understanding the dynamic nature of brain activity and its underlying circuit and molecular mechanisms
requires tools to monitor and control specific parts of the brain (e.g. regions, circuits, cells, synapses, or
molecules). Our group monitors brain activity by employing a variety of approaches, including in vivo fluorescence
imaging, neuropixels, and molecular engineering. We also design optogenetic tools and synthetic proteins to
control specific cellular and molecular functions in the brain with high spatiotemporal precision.
In conjunction with efforts to develop novel behavior paradigms in animals, we seek to identify important
operating mechanisms at the molecule-circuit-organism level that underlie cognition and social interaction.
Communication across various scales of biological systems, from molecules to organisms, is essential for sharing information among members of society. At the molecular level, communication among a particular set of molecules is important not only to determine the functions and fates of individual cells but also to create harmonious and complex multicellular actions such as brain circuit activity that can ultimately change organisms’ behaviors. Therefore, understanding the nature of molecular communication and its impact on higher-level communication is a fundamental step toward explaining how the brain works as a whole. To achieve this, we design a variety of synthetic molecules by employing and combining naturally occurring or engineered proteins to visualize or control molecular and cellular communication in living organisms. During the last decade, we have developed genetically encoded fluorescent sensors to assess molecular interactions in live cells and visualize protein activity at the subcellular level in the brain of behaving animals. Besides molecular sensors, we have also developed a series of optogenetic tools to control diverse intracellular molecules including calcium channels, receptor tyrosine kinases, cytoskeleton proteins, and mRNAs.
We are now moving towards focusing on intercellular communication in the brain to elucidate the role of cell-cell interaction in various brain functions such as cognition, learning and memory, and social behaviors. To this end, we are developing novel molecular tools to visualize or control different types of cell-cell interactions or their molecular mediators (e.g. neuro/gliotransmitters, peptides, or proteases). We believe that these technologies will open new avenues to deepen our understanding of how molecular communication can be translated into higher-level
function in the brain and how its dysfunction causes various brain disorders
Synthetic biology, Protein engineering, Molecular optogenetics, Molecular and cellular interaction
Within a close-knit social group, recognizing an individual as a unique identity and associating and retrieving individual-specific information during social interactions are fundamental abilities for living as a member of the group. Although individual recognition has been reported in many different species, including rodents, its neural underpinnings remain unclear. We have been developing simplified and precisely controlled individual discrimination paradigms in which subject mice distinguish between stimulus mice based on their individually unique characteristics. Together with quantitative behavioral measures, we use multiple state-of-art techniques, including two-photon calcium imaging, miniscope imaging, and Neuropixels recordings, to reveal neural mechanisms of social recognition.
Social information processing and memory formation, Episodic information processing, Ensemble perception