Masashi Tabuchi, PhD

Assistant Professor
Department of Neurosciences
School of Medicine

Teaching Information

Office Hours

Research Information

Research Interests

How do neurons generate information to drive behavior? The Tabuchi lab's overarching goal is to elucidate how neural coding impacts molecular/cellular signaling, plasticity, and behavior. We employ multidisciplinary approaches, leveraging both Drosophila models and human iPS cell-derived neurons. Through our research in Drosophila, we can precisely and rapidly identify significant phenotypes, and then validate the conservation of these phenotypes in human iPS cell-derived neurons. The phenotype identification process involves the use of state-of-the-art data acquisition methods, including patch-clamp electrophysiology, multi-electrode array and FRET functional imaging, arousal/sleep measurements, as well as our sophisticated machine learning platforms that aid in the construction of mathematical models to extract features of the temporal structure of neural activity patterns. We believe this approach is novel and will garner significant attention worldwide. Our research scope encompasses hierarchical interactions of gene expression, biophysical properties such as ionic currents, temporal structure of membrane potential dynamics including spiking patterns, functional synaptic connectivity of neural circuits, and behavior. We aim to answer fundamental questions such as the determining factors of processing performance in neural circuits, the molecular and cellular events underlying these factors, and their modulation of neuronal, synaptic, and behavioral states. By addressing these questions, we anticipate gaining key insights into the principles of neural codes underlying the persistent internal drive of the brain and providing a framework to understand how these factors contribute to overall health.

Research Projects

1. Circadian Clock Neural Encoding Mechanisms Engineering Sleep
Our research focuses on understanding the relationship between sleep quality and neural coding. Sleep quality is influenced by clock-driven temporal coding within arousal circuits (Tabuchi et al., 2018), and previous work in our lab has revealed age-related unstructured patterns of this temporal coding (Nguyen et al., 2022). We have also elucidated the molecular and biophysical mechanisms underlying the impact of downstream arousal circuits on temporal codes, identifying a novel form of synaptic plasticity driven solely by the temporal pattern of spiking (Tabuchi et al., 2023). Our current investigations aim to explore how neural codes affect molecular/cellular signaling to regulate sleep quality, employing techniques such as in vivo intracellular and extracellular electrophysiology, in vivo functional imaging, optogenetics, and sophisticated behavioral analysis.

2. Molecular and Neural Mechanisms of Nutrition-Specific Hunger
Our lab has identified the first neural circuit encoding protein-specific hunger (named DA-WED neurons) and demonstrated their critical role in protein hunger in Drosophila. Through a combination of molecular, genetic, computational, and electrophysiological approaches, we seek to understand how the temporal structure of membrane potential serves as non-canonical (temporal or analog) neural codes in DA-WED neurons for the persistent internal drive of nutrition-specific hunger/satiety.

3. Molecular and Neural Mechanisms of Alzheimer's Disease
We aim to uncover novel pathological mechanisms of Alzheimer's disease by integrating research in both Drosophila and human iPS cell-derived neurons. Leveraging Drosophila models allows us to rapidly capture behaviorally relevant molecular phenotypes of Alzheimer's disease, which we then validate in human iPS cell-derived neurons. Our advanced data acquisition methodologies, including simultaneous electrophysiology and arousal/sleep measurements, coupled with sophisticated machine learning platforms, enable us to construct mathematical models extracting features of the temporal structure of neural activity patterns. Our study will address gaps in the understanding of how alterations in computational biophysical states contribute to Alzheimer's disease and related tauopathies, particularly in the context of circadian regulation of sleep, and pave the way for the development of novel therapeutic strategies.

4. Neurotechnology Development
We are interested in developing novel electrophysiological methods to facilitate long-term stable measurements of neuronal activity. Electrophysiological recording with glass electrodes remains one of the most effective techniques for measuring membrane potential dynamics and ionic currents of voltage-gated channels in neurons. We have pioneered the development of a phospholipid membrane coating on glass electrodes to improve the quality of intracellular electrophysiological recordings (Jameson et al., 2024), and we are exploring ways to extend this technology to various other electrode types. Our lab specializes in using a range of state-of-the-art tools and techniques to delve deeper into the neural mechanisms underlying behavior. The emphasis on these technologies underscores our commitment to pushing the boundaries of neuroscience research and highlights the diverse opportunities available to students and researchers in our lab.

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Awards and Honors

Neuroscience Society Young Investigator Award
2023
Japan Neuroscience Society
Scialog Molecular Basis of Cognition Fellow
2022
Research Corporation for Science Advancement
NIGMS Maximizing Investigators' Research Award (R35 MIRA Award)
2021
National Institute of General Medical Sciences
Whitehall Foundation Fellow
2021
Whitehall Foundation
Outstanding Early Investigator Award
2019
Sleep Research Society
Daniel Nathans Young Investigator Award
2019
Johns Hopkins School of Medicine

Publications

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Selected Publications

Jameson AT, Spera LK, Nguyen DL, Paul EM, Tabuchi M. (2024). Membrane-coated glass electrodes for stable, low-noise electrophysiology recordings in Drosophila central neurons. Journal of Neuroscience Methods. in press

Tabuchi M. (2023). Dynamic Neuronal Instability Generates Synaptic Plasticity and Behavior: Insights from Drosophila Sleep. Neuroscience Research 198:1-7.

Nguyen DL, Hutson AN, Zhang Y, Skylar DD, Peard AR, Tabuchi M. (2022). Age-Related Unstructured Spike Patterns and Molecular Localization in Drosophila Circadian Neurons. Frontiers in Physiology 13:845236.

Tabuchi M, Monaco JD, Duan G, Bell BJ, Liu S, Liu Q, Zhang K, Wu MN. (2018). Clock-Generated Temporal Codes Determine Synaptic Plasticity to Control Sleep. Cell 175(5): 1213-1227.

Liu Q*, Tabuchi M* (co-first author), Liu S, Kodama L, Horiuchi W, Daniels J, Chiu L, Baldoni D, Wu MN. (2017). Branch-Specific Plasticity of a Bifunctional Dopamine Circuit Encodes Protein Hunger. Science 356, 534-539.

Tabuchi M, Lone SR, Liu S, Liu Q, Zhang J, Spira AP, Wu MN. (2015). Sleep Interacts with Aβ to Modulate Intrinsic Neuronal Excitability. Current Biology 25(6):702-712.

Education

Doctor of Philosophy
The University of Tokyo
2013
Postdoctoral Fellowship
Johns Hopkins University
2019