I am deeply honored to receive the prestigious Toshihiko Tokizane Award. I would like to express my heartfelt gratitude to the members of the selection committee, the professors who have guided me throughout my career, the collaborators, and the many members of my laboratory who have worked alongside me on this research.

It was in 1989 that I first became fascinated by the world of olfaction. After completing my Ph.D. program at the Graduate School of Pharmaceutical Sciences of Kyoto University, I joined the Department of Neuroscience, Osaka Bioscience Institute, as a postdoctoral researcher. At the time, Dr. Kensaku Mori (then Deputy Director; now Professor Emeritus at The University of Tokyo) was conducting immunohistochemical experiments right next to my bench. Although I was just a novice researcher, Dr Mori -who was already a leading authority in olfactory research- kindly and patiently taught me the fundamentals of brain science, particularly neuroanatomy and physiology. He also included me in discussion about “the odor map in the olfactory bulb”, a concept that had not yet been published at the time. Since Buck and Axel published their paper on the discovery of olfactory receptor multigene family in 1991, I was fortunate enough to be quietly taught the answer to the fundamental question in olfactory research -“How is olfactory information represented in the brain?”- two years prior. Furthermore, visiting the laboratories of Gordon Shepherd and Richard Axel in 1991, and subsequently interacting with many young scientists who would go on to lead the field of olfactory research, was a transformative experience that marked the beginning of my deep immersion in the field. In this way, I found myself completely engrossed in the world of olfactory research right at its dawn.

From the 1990s to the 2000s, the olfactory research mainly centered on a molecular-based strategy (molecule → cell → circuit → behavior). Beginning with the discovery of olfactory receptor genes, researchers identified signaling molecules involved in odor reception and molecules governing the formation of the primary olfactory circuit from the olfactory epithelium to the olfactory bulb. Using mice as a model organism and employing molecular biology, biochemistry, and gene engineering techniques, we discovered novel molecules playing important roles in the olfactory system, such as Telencephalin, OCAM, BID-1, BIG-2 and Goofy, and also identified groups of axon guidance molecules and transcription factors that function in the wiring of olfactory circuits. These findings, combined with the work of other researchers, have contributed to elucidating the overall molecular mechanisms underlying the formation and function of the primary olfactory system.

However, by the late 2000s, I began to sense the limitations of molecule-based olfactory research and initiated a completely opposite approach based on diverse olfactory behaviors: I aimed to elucidate the molecular, cellular and circuit mechanisms underlying various olfactory behaviors. By employing zebrafish as a model organism, this strategy proved successful, revealing neural mechanisms for the attraction to amino acids and ATP emitted by food sources, the courtship behavior exhibited by male fish in response to prostaglandin F2α secreted by ovulating female fish, the avoidance in response to high concentration of carbon dioxide¹⁹, and the alarm reaction that warn conspecifics of danger via Schreckstoff secreted from the skin of injured fish. In addition, we have successfully developed a genetic method for single-neuron visualization of the secondary olfactory pathway from the olfactory bulb to higher-order centers. Furthermore, the transsynaptic neural circuit tracing technology using WGA transgene which we developed in parallel with the olfactory research has been effectively utilized by many researchers in various model organisms ranging from invertebrates to primates.

On a different note, deep within the cerebral cortex of all mammals including humans, there exists a thin, sheet-like structure called the “claustrum”. Because the claustrum has reciprocal connections with all the neocortical areas, it has been suggested that the claustrum may be involved in global higher-order brain functions, and numerous hypotheses have been proposed regarding its role in the multisensory integration, the attentional load allocation, and the control of synchronized brain activities. Particularly, in his final review article published in 2005, Francis Crick put forward the bold hypothesis that “the claustrum might be the seat of consciousness”, yet the true nature of the claustrum’s function remained shrouded in mystery. Around 2010, we were generating numerous transgenic mouse lines expressing fluorescent proteins or DNA recombinase Cre in various types of neurons along the olfactory circuit when we accidentally discovered that Cre was expressed specifically in the claustral neurons in one of these lines. It was truly serendipity. In these mice, when channelrhodopsin was expressed selectively in the claustrum and these neurons were excited by light stimulation, synchronous firing of inhibitory neurons in the cerebral neocortex occurred, followed by “down state” of neural activities in widespread cortical areas lasting approximately 150 msec. This suggests that the claustrum may be involved in inducing synchronous neural activities throughout the cortex and, furthermore, in regulating the level of consciousness. Moving forward, we plan to use this mouse line and employ neural circuit genetic techniques to validate Crick’s hypothesis, aiming to clarify the function of the claustruma and elucidate the neural mechanisms of consciousness.