N. Charles Harata, MD, PhD
Introduction
My laboratory focuses on the study of synaptic transmission in the mammalian central nervous system. Synapses are the sites at which electrical signals that have been transmitted through presynaptic neurons are converted to chemical signals (neurotransmitter release). The neurotransmitter released at these sites induces responses in the postsynaptic neuron – in the form of both electrical and chemical signals (such as an increase in the intracellular calcium concentration). The efficiency of this two-step information flow during synaptic transmission is vital to the control of neural network activity, and we are currently focusing on two projects related to this control of synaptic transmission.
In one project, we are evaluating the fundamental parameters of neurotransmitter release from the presynaptic site, including: the amount of neurotransmitter loaded into synaptic vesicles, and the variability in the rate of neurotransmitter release. We study them by applying the electrophysiological technology, live-cell wide-field fluorescence imaging, super-resolution fluorescence imaging and electron microscopy to the cultured brain neurons of wild-type rodents.
In another project, we are elucidating the cellular pathophysiology of a movement disorder dystonia. Dystonia is characterized by involuntary skeletal muscle contractions and abnormal postures. It causes extensive deterioration of the patient's quality of life. In some patients, this condition becomes life threatening (dystonic storm), with excessive muscle contractions leading to an inability to swallow or breathe, and to skeletal muscle breakdown and multi-organ failure. Unfortunately, there is no effective cure, and treatment options are limited. Our study addresses the synaptic abnormalities in the brain, especially in the rates of synaptic vesicle recycling and neurotransmitter release, the regulation of intracellular calcium signals, and the structures of synapses and intracellular organelles.
Current Positions
- Associate Professor of Molecular Physiology and Biophysics
Education
- MD, Tohoku University School of Medicine, Sendai, Japan
- PhD in Neuropathology, Tohoku University School of Medicine, Sendai, Japan
- Postdoctoral Fellow, Japan Society for the Promotion of Science, Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan
- Postdoctoral Fellow, Department of Molecular & Cellular Physiology, Stanford University School of Medicine
Graduate Program Affiliations
Center, Program and Institute Affiliations
Research Interests
- Mechanisms that Regulate Synaptic Transmission and how the Disregulation of Synaptic Transmission Contributes to Neurological and Psychiatric Disorders
Licenses & Certifications
- English Commission for Foreign Medical Graduates (ECFMG), National board of physicians, USA
- National board of physicians, Japan
Selected Publications
- Oyabu K, Takeda K, Kawano H, Kubota K, Watanabe T, Harata NC, Katsurabayashi S, Iwasaki K. Presynaptically silent synapses are modulated by the density of surrounding astrocytes. J Pharmacol Sci. 2020 Oct;144(2):76-82. doi: 10.1016/j.jphs.2020.07.009. Epub 2020 Jul 24. PMID: 32736867.
- White S, Kawano H, Harata NC, Roller RJ. Herpes Simplex Virus Organizes Cytoplasmic Membranes To Form a Viral Assembly Center in Neuronal Cells. J Virol. 2020 Sep 15;94(19):e00900-20. doi: 10.1128/JVI.00900-20. PMID: 32699089; PMCID: PMC7495378.
- Kawano H, Mitchell SB, Koh JY, Goodman KM, Harata NC. Calcium-induced calcium release in noradrenergic neurons of the locus coeruleus. Brain Res. 2020 Feb 15;1729:146627. doi: 10.1016/j.brainres.2019.146627. Epub 2019 Dec 27. PMID: 31883849.
- Mitchell SB, Iwabuchi S, Kawano H, Yuen TMT, Koh JY, Ho KWD, Harata NC. Structure of the Golgi apparatus is not influenced by a GAG deletion mutation in the dystonia-associated gene Tor1a. PLoS One. 2018 Nov 7;13(11):e0206123. doi: 10.1371/journal.pone.0206123. PMID: 30403723; PMCID: PMC6221310.
- Beauvais G, Bode NM, Watson JL, Wen H, Glenn KA, Kawano H, Harata NC, Ehrlich ME, Gonzalez-Alegre P. Disruption of Protein Processing in the Endoplasmic Reticulum of DYT1 Knock-in Mice Implicates Novel Pathways in Dystonia Pathogenesis. J Neurosci. 2016 Oct 5;36(40):10245-10256. doi: 10.1523/JNEUROSCI.0669-16.2016. PMID: 27707963; PMCID: PMC5050323.
- Iwabuchi S, Kakazu Y, Koh JY, Goodman KM, Harata NC. Examination of synaptic vesicle recycling using FM dyes during evoked, spontaneous, and miniature synaptic activities. J Vis Exp. 2014 Mar 31;(85):50557. doi: 10.3791/50557. PMID: 24747983; PMCID: PMC4160174.