Dr. Tatsuya Tsukahara

PRINCIPAL INVESTIGATOR

One of the most fascinating features of the living cells is the ability to modulate their functions based on experience. For example, in the nervous system, neurons that have been highly active attenuate their responses to stimuli, whereas recently inactive neurons boost responses. Dr. Tatsuya Tsukahara seeks the logic by which neurons use the molecular language—in forms of altered gene and protein expression—to encode experience and optimize neural and circuit functions.

Dr. Tsukahara has used the mammalian olfactory system as a primary model. By using single-cell RNA-sequencing and in vivo calcium imaging, his postdoctoral work revealed that olfactory sensory neurons in the nose dramatically reconfigure their transcriptomes to adapt over timescales of hours to days.

This long-term and transcriptional adaptation in the peripheral neurons contrasts with well-known forms of adaptation, which is achieved in the brain through modulation of firing frequency and synaptic weights on relatively short timescales like seconds to minutes.

To understand general principles of adaptation in the nervous system, Dr. Tsukahara’s laboratory pursues two fundamental questions: What are the molecular mechanisms through which neurons encode experience sculpted by signals from the outside world and ones from inside of the body that signify internal states or life stages to optimize cellular functions? How does adaptation at the periphery impact the brain circuits and behavior in healthy and pathological conditions?

His laboratory uses cutting-edge technologies including single-cell and spatial transcriptomics and proteomics, calcium and voltage imaging, optogenetics and chemogenetics, and computational behavioral analyses.

Dr. Tsukahara initially trained at the University of Tokyo. He received his PhD performing research on molecular mechanisms of chromosome segregation and motile cilia formation, and then became a junior group leader in Dr. Hiroyuki Takeda’s laboratory to study epigenetic gene regulation in pluripotent embryos and adult tissues.

As his interest expanded to a more adaptive system, he started neuroscience research in Dr. Bob Datta’s laboratory at Harvard Medical School, where he worked on transcriptional adaptation in the olfactory sensory neurons, exploring the mechanisms of COVID-19 induced anosmia, and machine learning-based behavioral analyses of autism model mice.

He was recruited to the LTRI in September 2023.

At a Glance

Investigator at Lunenfeld-Tanenbaum Research Institute and Assistant Professor at the Department of Molecular Genetics, University of Toronto

Studies adaptation in the mammalian nervous system, which allows neurons and neural networks to flexibly modulate their functions based on experience and optimize their functions

Takes approaches at the intersection of neuroscience and systems biology including single-cell transcriptomics, in vivo imaging, and optogenetics

Awarded Y. Eva Tan Postdoctoral Fellowship at the Hock E. Tan and K. Lisa Yang Center for Autism Research at Harvard University and the GE & Science Prize for Young Scientist Regional Winner for Asia

Major Research Activities

Dr. Tsukahara is interested in how neurons encode their experience in forms of gene and protein expression and modulate their functions, and ultimately optimize the brain circuits and animal behavior. His lab focuses on:

1. Dissecting the molecular mechanisms that couple neural activity, gene expression, and neural functions

2. Examining how peripheral sensory neurons respond to the signals from inside of the body like hormones and integrate them with the signals from the outside world

3. Characterizing how the transcriptional adaptation in peripheral neurons impacts the brain circuits and behavior in healthy, aged, and disease conditions

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Dr. Tatsuya Tsukahara

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