DEPARTMENT OF CEREBRAL RESEARCH

The transmission of information in the brain is controlled and regulated by various functional molecules, including receptors, channels and transporters located on the plasma membrane of neuronal and glial cells. The main purpose of this division is to investigate the functional roles of these molecules in the synaptic transmission, neuronal circuits, systematic organization of the brain and animal behaviors, by analyzing their localization, movements, and functions using morphological, electro­physiological, and molecular biological techniques. Special attentions are being made to combine these different techniques efficiently and elucidate the integrated brain functions.
The main projects are as follows.

(1) Ultrastructural analysis of the localization of glutamate and GABA receptors, especially in spatial relation to the synapses, and colocalization of these receptors with various channel molecules regulated by receptor activation. Visualization of these functional molecules in the plastic changes, or pathological conditions, using in vitro model systems as well as in vivo. For example, we have recently found colocalization of various subunits of glutamate (Fig.1) and GABA receptors using a newly developed SDS-digested freeze-fracture replica labeling method. This method is highly sensitive and useful for quantification of number and density of receptor and channel molecules. Recently, we are also working on left-right asymmetry of NMDA receptors to clarify its physiological significance and mechanism of its formation.

(2) Analysis of synaptic transmission and its modulation in nigro-striatal or mesolimbic dopaminergic system (Fig.2), and cholinergic system in the basal forebrain. These systems are involved in various psychological functions. The regulation of output from these systems to cerebral cortex is also studied.
Another issue is the analysis of pain-perception systems in the spinal cord or brain stem. These studies are carried out using mainly slice-patch-clamp technique. The molecular bases of these mechanisms are also being elucidated.

(3) Analysis of the effect of dynamic changes in synaptic and glialmicroenvironment to the spatiotemporal distribution of neurotransmitters. It has been shown that ectopic release of synaptic vesicles occurs from presynaptic terminals directly facing the surrounding glial cells in the cerebellum (Fig.4). Preliminary data of two-photon imaging show that such form of neural-glial communication may mediate rapid remodeling of the microenvironment. We will analyze how the glial encasement of synaptic structures affects synaptic transmission using combinations of electrophysiological and EM methods.

Fig.1 Co-localization of AMPA-type (5nm gold particles) and GluRd2 (10nm gold particles) glutamate receptors in the cerebellum

Fig.2 Asymmetrical allocation of NMDA receptors in the hippocampus

Fig.3 Presynaptic inhibition of GABA release in basal ganglia synapses by dopamine

Fig.4 Simultaneous recording of Ca increase and current response to synaptic stimuli in glial cells

Staff

	Professor: SHIGEMOTO, Ryuichi, MD, PhD 1985 Graduated from Kyoto University Faculty of Medicine. 1986 Resident, Kyoto University Hospital. 1989 Instructor, Kyoto University Faculty of Medicine. 1998 Professor, NIPS. Speciality: Neuroanatomy and molecular neuroscience
	Associate Professor: MOMIYAMA, Toshihiko, MD, PhD 1988 Graduated from Kyoto University Faculty of Medicine. 1990 Instructor, Kyoto University Faculty of Medicine. 1994 Postdoctoral Fellow, University College London. 1996 Assistant Professor, Nagasaki University School of Medicine. 1999 Associate Professor, NIPS. Speciality: Neurophysiology and neuropharmacology
	Assistant Professor: FUKAZAWA, Yugo, PhD 1988 Graduated from Yokohama City University Faculty of Science. 1997 Completed the doctoral course in Science. 1997 Postdoctoral fellow, Mitsubishi Kagaku Institute of Life Sciences. 2001 Assistant Professor, NIPS. Speciality: Molecular neuroscience, Endocrinology
	Assistant Professor: MATSUI, Ko, PhD 1996 Graduated from University of Tokyo, Department of Psychology. 2001 Completed the doctoral course in Psychology at University of Tokyo. 2001 Postdoctoral Fellow at Oregon Health & Science University. 2006 Assistant Professor at NIPS. Speciality: Neurophysiology
	Research Associate: KAMASAWA, Naomi, PhD 1988 Graduated from Japan Women’s University. Researcher, Mitsui Chemical Inc. 2002 Assistant professor, Japan Women’s University. 2003 Visiting Scientist & Research Assistant Professor, Colorado State University. 2007 Research Associate at NIPS. Speciality: Neuroanatomy
	Postdoctoral Fellow: KASUGAI, Yu, PhD 2006 Graduated from School of Life Science, the Graduate University for Advanced Studies. 2006 Postdoctoral Fellow at NIPS. Speciality: Neuroanatomy
	Postdoctoral Fellow: TARUSAWA, Etsuko, PhD 2006 Graduated from School of Life Science, the Graduate University for Advanced Studies. 2006 Postdoctoral Fellow at NIPS. Speciality: Neuroanatomy
	Postdoctoral Fellow: KAWAKAMI, Ryosuke, PhD 1997 Graduated from Kyushu University, Faculty of Science. 2003 Completed the doctoral course in Medicine at Kyushu University. 2003 Postdoctoral Fellow at Kyushu University. 2005 Postdoctoral Fellow at NIPS. Speciality: Neurophysiology
	Foreign Research Fellow: DONG, Yulin, MD, PhD 1999 Graduated from Weifang medical Institute, Faculty of medicine (China). 2005 Completed the doctoral course in Neurobiology, Lecturer, Department of Anatomy, Fourth Military Medical University, Xi’an. 2007 Postdoctoral Fellow at NIPS. Speciality: Neuroanatomy

The neocortex is composed of many functionally-differentiated areas to support the complex activities such as perception, movement and thinking. To understand the function of the cortex, the knowledge of the internal structure of a functional unit in each area is necessary, but not well elucidated yet. Although several types of neurons are involved in the cortical function, the way of information processing in each type of cells and the connection rules among them have not been well understood. Different types of neurons release different chemical substances. How each substance affects the activity of local circuits also need to be understood.

The research in this laboratory concerns the structural and functional analysis of the internal circuits of the cerebral cortex. Physiological characterization of local circuit neurons, functional unit structures in local circuits, and connectional paths among neuronal subtypes will be investigated by electrophysiological, immunohistochemical and morphological techniques to establish the fundamental basis for modeling of the cortical circuitry.

In parallel with functional classification of GABAergic nonpyramidal cells and pyramidal cells projecting to the other cortical areas, striatum or brainsten, we are investigating the physiological properties of synaptic transmission of each type and their synaptic connections quantitatively in the cortex.

Summary of phasic actions of ACh on neocortical neurons. Above, Diagram showing several classes of neocortical neurons and their responsiveness to ACh. Red upward arrows indicate cell-types exhibiting nAChR-mediated excitation to focal ACh application while blue downward arrows indicate cell-types inhibited via mAChR activation. Below, Representative traces showing the effect of ACh on the various cell-types shown in above.

Synaptic innervations of cortical spines. A, A cortical spine (Sp) was coinnervated by a VGLUT2-positive (T2) asymmetrical synapse (black arrow) and two symmetrical synaptic terminals (white arrows). B, Schematic summary of the GABAergic input to dendritic spines. Most VGLUT1-positive axon terminals originate from cortical cells (purple) and innervate spines of cortical pyramidal neurons (gray) that receive no secondary synaptic input. VGLUT2-positive axon terminals (green) originate from the thalamus and innervate larger spine heads of pyramidal cells (gray) that exhibit a second, GABAergic synaptic input (orange) in 10% of cases.

Staff

	Professor: KAWAGUCHI, Yasuo, MD, PhD 1980 Graduated from the University of Tokyo, Faculty of Medicine. 1984 Research Associate, NIPS. 1985 Completed the doctoral course at the University of Tokyo.1987 Research fellow, University of Tennessee. 1989 Research fellow, RIKEN.1993 Laboratory head, RIKEN. 1999 Professor, NIPS. Speciality: Neuroscience
	Associate Professor: KUBOTA, Yoshiyuki, PhD Graduated from the master course (1984) and doctor course (1988) at Osaka University, Faculty of Medicine. 1989 Research fellow, University of Tennessee, Dept Anatomy and Neurobiology. 1990 Research Associate, Kagawa Medical School. 1991 Research fellow, RIKEN. 2001 Associate Professor, NIPS. Speciality: Neuroanatomy, Neuroscience
	Assistant Professor: OTSUKA, Takeshi, PhD 1997 Graduated from Osaka University, Faculty of Engineering Science. 1999 Graduated from the master course at Osaka University, Graduate School of Engineering Science. 2002 Graduated from the doctoral course at the Osaka University, Graduate School of Engineering. 2002 Research Associate, Duke University Medical Center. 2004 Assistant Professor, NIPS. Speciality: Neuroscience
	Assistant Professor: MORISHIMA, Mieko, PhD 1999 Graduated from Tokyo University of Pharmacy and Life Science.2001 Completed the master course in Osaka University. 2006 Completed the doctoral course in The Graduate University for Advanced Studies. 2006 Postdoctoral fellow,　NIPS. 2006 Assistant Professor. Speciality:Neuroscience
	Postdoctoral Fellow: SHIGEMATSU, Naoki, PhD 2002 Graduated from Nagasaki University, School of Pharmaceutical Sciences. 2004 Graduated from the master course at the Kyushu University, Graduate school of Pharmaceutical Sciences. 2007 Graduated from the doctoral course at the Kyushu University Graduate school of Pharmaceutical Sciences. 2007 Research fellow, NIPS. Speciality: Neuroscience

The goal of Division of Cerebral Integration is to understand the physiology of human voluntary movement and other mental processing including language using noninvasive functional neuroimaging technique, mainly fMRI. In particular, understanding of the mechanisms of plastic change in the human brain accompanied by learning, sensory deafferentation, and development is the main focus of our research activities. Multimodality approach including EEG , MEG , TMS , and NIR is considered when appropriate.

Figure 1.Activation in a sighted (upper row) and blind subject (bottom row) during tactile discrimination tasks similar to reading Braille. The primary and association visual cortices of the blind are activated bilaterally (bottom row) whereas no such activation in the sighted. Only pixels with significant increase in cerebral blood flow during the task were superimposed on surface-rendered high resolution MRI. This is an example of cross-modal plasticity of human brain due to early visual deafferentation and/or long-term training of Braille reading. Depicted by functional MRI using high Tesla (3T) machine.

Figure 2 Brain areas for implicit and explicit learning. There are two different way of acquisition of knowledge, implicit learning and explicit learning. Implicit learning is characterized as an unintentional, un-conscious form of learning recognized behavioural improvement (such as shortening of reaction time). Explicit learning involves conscious recollection of previous experiences. In a serial reaction time task, subjects pressed each of four buttons with a different finger of the right hand in response to a visually presented number. Explicit learning was associated with increased activity in the frontoparietal networks (Upper row). During the implicit learning phase, when the subjects were not aware of the sequence, improvement of the reaction time was associated with increased activity in the contralateral primary sensorimotor cortex (Bottom row). These results show that different sets of cortical regions are dynamically involved in implicit and explicit motor sequence learning.

Staff

	Professor: SADATO, Norihiro, MD, PhD 1983 Graduated from Kyoto University School of Medicine. 1994 Completed the doctoral course in Medical Sciences, Kyoto University. 1993-95 Visiting Research Fellow, NINDS, NIH. 1995 Lecturer, Fukui Medical University. 1998 Associate Professor, Fukui Medical University. 1999 Professor, NIPS. Speciality: Functional neuroimaging
	Associate Professor: SUGIURA, Motoaki, MD, PhD 1996 Graduated from Tohoku University School of Medicine. 2000 Completed the doctoral course in Medical Sciences, Tohoku University. 2000 Research Fellow, 2001 Assistant Professor, Tohoku University. 2002-04, Gastwissenschaftler, Institut für Medizin, Forschungszentrum Jülich (Postdoctoral Fellowship for Research Abroad, JSPS). 2004 Associate Professor, Miyagi University of Education. 2006 Associate Professor, NIPS. Speciality: Functional neuroimaging
	Assistant Professor: TANABE, Hiroki, PhD 1991 Graduated from College of Liberal Arts, International Christian University. 1998 Completed the doctoral course in Medical Sciences, Osaka University. 1998 Research Fellow, Communications Research Laboratory. 2002 JST Research Fellow. 2004 Assistant Professor, NIPS. Speciality: Cognitive Brain Science
	Postdoctoral Fellow: TOYODA, Hiroshi, MD, PhD 1994 Graduated from Faculty of Medicine, Kyoto University. 2002 Completed the doctoral course in Medical Sciences, Kyoto University Graduate School of Medicine. 2003 Postdoctoral Fellow, NIPS. 2006 JST Research Fellow. Specialty: Functional neuroimaging
	Postdoctoral Fellow: SAITO, Daisuke, PhD 1996 Graduated from Faculty of Integrated Arts and Sciences, Tokushima University. 1998 Completed the master course in Human and Natural Enviroment Sciences,Tokushima University. 2003 Completed the doctoral course in Medical Sciences, Tokushima University. 2002 Fellow, NIPS. 2005, JST Research Fellow. Speciality: Functional neuroimaging
	Postdoctoral Fellow: MATSUMOTO, Atsushi, MA 2002 Graduated from Department of Psychology, Nagoya University. 2004 Completed the master course in Graduate School of Environmental Studies, Nagoya University. 2007 Completed the doctoral course in Graduate School of Environmental Studies, Nagoya University. 2007-JSPS Research Fellow. Speciality: Neuroscience, Psychophysiology
	Postdoctral Fellow: KOMEDA, Hidetsugu, PhD 2002 Graduated from Faculty of Arts and Letters, Tohoku University.2004 Completed the master course in Graduate School of Education, Kyoto University. 2007 Completed the doctoral course in Graduate School of Education, Kyoto University. 2005 JSPS Doctoral Course Fellow. 2007 JSPS Postdoctoral Research Fellow. Speciality: Cognitive psychology, Social cognitive neuroscience
	Postdoctoral Fellow: MURASE, Mika, PhD 1999 Graduated from Tokyo University of Agriculture, Faculty of Agriculture. 2004 Completed the master course, Graduate School of Education, Fukui University. 2007 Completed the doctoral course in Life Science, The Graduate University for Advanced Studies. 2007 Postdoctoral fellow, NIPS. Speciality: Neuroscience