Introduction

Dr. Kenji Tanaka is studying how the brain works. He looks at how the brain is made up of many layers. These layers include genes, cells, circuits, and behavior. He also thinks of the brain as all the neurons, glia, and blood vessels in the body, which work together with the organs outside the brain. He is using this view and animal models to answer two main questions: "Why do people develop mental disorders?" and "Why do people recover from mental disorders?"

■ Development of Research Methods and Tools
He has constructed an experimental system to observe and manipulate cell functions with spatial and temporal precision in mice.
・Research objective: Gene manipulation
- Title：Flexible Accelerated STOP Tetracycline Operator-Knockin (FAST): A Versatile and Efficient New Gene Modulating System. Tanaka KF, Ahmari SE, Leonardo ED, Richardson-Jones JW, Budreck EC, Scheiffele P, Sugio S, Inamura N, Ikenaka K, Hen R. Biol Psychiatry. 67:770-773, 2010
・Research objective: Channelrhodopsin expressing mice.
- Title：Expanding the repertoire of optogenetically targeted cells with an enhanced gene expression system. Tanaka KF, Matsui K, Sasaki T, Sano H, Sugio S, Fan K, Hen R, Nakai J, Yanagawa Y, Hasuwa H, Okabe M, Deisseroth K, Ikenaka K, Yamanaka A. Cell Rep 2(2):397-406, 2012
・Research objective: Ratiometric Ca sensor expressing mice.
- Title：In Vivo visualization of subtle, transient, and local activity of astrocytes using an ultrasensitive Ca(2+) indicator. Kanemaru K, Sekiya H, Xu M, Satoh K, Kitajima N, Yoshida K, Okubo Y, Sasaki T, Moritoh S, Hasuwa H, Mimura M, Horikawa K, Matsui K, Nagai T, Iino M, Tanaka KF.Cell Rep 8:311-318, 2014
・Research objective: Vascular optogenetics.
- Title：Optical manipulation of local cerebral blood flow in the deep brain of freely moving mice. Abe Y, Kwon S, Oishi M, Unekawa M, Takata N, Seki F, Koyama R, Abe M, Sakimura K, Masamoto K, Tomita Y, Okano H, Mushiake H, Tanaka KF. Cell Rep. 36(4):109427. 2021

■Behavioral Neuroscience Research
He has developed techniques to observe the activity of specific neurons in freely moving mice, and to manipulate the given activities to address causal relationship between cell function and behavior.
・Research objective: Apathy model mice (impaired motivation)
- Title：Dysfunction of ventrolateral striatal dopamine receptor type 2-expressing medium spiny neurons impairs instrumental motivation. Tsutsui-Kimura I, Takiue H, Yoshida K, Xu M, Yano R, Ohta H, Nishida H, Bouchekioua Y, Okano H, Uchigashima M, Watanabe M, Takata N, Drew MR, Sano H, Mimura M, Tanaka KF. Nat Commun 8: 14304, 2017
・Research objective: Action initiation in motivated behaviors.
- Title：Ventrolateral Striatal Medium Spiny Neurons Positively Regulate Food-Incentive, Goal-Directed Behavior Independently of D1 and D2 Selectivity. Natsubori A, Tsutsui-Kimura I, Nishida H, Bouchekioua Y, Sekiya H, Uchigashima M, Watanabe M, de Kerchove d'Exaerde A, Mimura M, Takata N, Tanaka KF. J Neurosci. 37(10):2723-2733, 2017
・Research objective: Action sustainment in motivated behaviors.
- Title：Serotonin-mediated inhibition of ventral hippocampus is required for sustained goal-directed behavior. Yoshida K, Drew MR, Mimura M, Tanaka KF. Nat Neurosci,
22(5):770-777, 2019
・Research objective: Role of serotonin in sleep
- Title：Oscillatory population-level activity of dorsal raphe serotonergic neurons is inscribed in sleep structure. Kato T, Mitsukura Y, Yoshida K, Mimura M, Takata N, Tanaka KF. J Neurosci. 42(38):7244-55. 2022

■ Neuroanatomical studies focusing on structural changes in the brain
He established a method to detect brain structural changes by using MRI and identify the subcellular changes by using super-resolution microscopy. 　　　　　　　　
・Research objective: Common pathology in dyskinesias.
- Title：Shared GABA transmission pathology in dopamine agonist- and antagonist-induced dyskinesia. Abe Y, Yagishita S, Sano H, Sugiura Y, Dantsuji M, Suzuki T, Mochizuki A, Yoshimaru D, Hata J, Matsumoto M, Taira S, Takeuchi H, Okano H, Ohno N, Suematsu M, Inoue T, Nambu A, Watanabe M, Tanaka KF. Cell Rep Medicine. 4(10):101208, 2023

■ Glial research
He has elucidated the neuron-glia interaction in health and disease.
・Research objective: Oligodendrocyte-mediated plasticity.
- Title：Oligodendrocytic Na+-K+-Cl- co-transporter 1 activity facilitates axonal conduction and restores plasticity in the adult mouse brain. Yamazaki Y, Abe Y, Fujii S, Tanaka KF. Nat Commun. 12(1):5146. 2021
・Research objective: Megalencephalic leukoenchephalopathy with subcortical cysts (MLC) model mice.
- Title：Astrocyte-mediated infantile-onset leukoencephalopathy mouse model. Sugio H, Tohyama K, Oku S, Fujiyoshi K, Yoshimura T, Hikishima K, Yano R, Fukuda T, Nakamura M, Okano H, Watanabe M, Fukata M, Ikenaka K, Tanaka KF. Glia 65 (1): 150-168, 2017

Areas of Research

Recovery of Mental Illness
Stress-Related Disorders (Depression, Anxiety)
Basal Ganglia Disorders
Glial Disease
Gene Therapy
Antidepressant Mechanisms of Action

Social Contributions

He will provide opportunities for society to consider the pros and cons of invasive brain interventions.
The mechanisms of stress resilience will be revealed.