Title: Logic of Neural Circuit Formation Instructed by the Peripheral Inputs
Summary: The aim of my research is to elucidate the logic of neural circuit formation that is specific to the higher animals, e.g., mammals. Although the neural circuits in the lower animals are mostly constructed by deterministic genetic programs, those in higher animals are more plastic and rely more on the peripheral information, including neuronal activity. I will study how the peripheral information determine the identity of individual neurons in higher brain regions and thereby help self-organize the neural circuits. To this end, I will also try to develop novel methods that enable genetic manipulation in a given neuronal column.

Title:Functional significance of adult neurogenesis
Summary:Discovery of neural stem cells and continuous neurogensis in the adult mammal brain has raised hope for a potential new strategy in utilization of endogenous mechanisms for brain repair. Research in my project is directed toward:  1. Development of genetic methods to control the behavior of newly generated neurons in the adult brain. 2. Understanding functional significance of continuous neurogensis in the adult brain, for future attempts in utilizing newly generated neurons for brain repair. 

Title: Functional analysis for the roles of "subcellular domains" in the migration and maturation of cortical immature neurons
Summary: Cells contain many "subcellular domains", such as organella and adhesion complexes, which are known to have some specific roles in cells, including neurons. However, in vivo roles of subcellular domains are still unclear. Neuronal circuit formation requires proper neuronal migration and maturation, both of which accompany dynamic cellular morphological changes and many subcellular events, suggesting the possible involvement of "subcellular domains" in these events. Now, I try to put neuronal migration and maturation in perspective of the "subcellular domain" functions. This novel approach may contribute to understand the mechanisms of cortical development and its related neurological disorders.

Title: Neural Networks to Control Specific Behavioral and Emotional Responses to the Smell
Summary: I pursue my original research on understanding the mechanisms that controls behavioral and emotional responses to smell in mammals at the level of neuronal circuit with genetic engineering. The emotional behavior is action of the mind which arouses essential instinct to survive. The results of this research show us the nonconventional point of view to understand our own minds.

Title: Construction of value information in the neural circuit of midbrain
Summary: I will examine the system dynamics of midbrain neural circuit during associative learning for reward/aversive events with electrophysiological approaches using primates based on mathematical theory, and clarify mechanism of coding of value information, maintenance of short-term memory and revision of memory for the learning process. I will explore basic algorithm of learning, mechanism of accessing and updating synaptic memory and computation of error signal to promote synaptic plasticity.

Title: Elucidation of the regulatory mechanism in cortical neuronal circuit operation by the inhibitory system
-Analysis by in vivo two-photon functional Ca2+ imaging and photostimulation-
Summary: For clarification of the brain function, it is very important to understand how the outside world is encoded in the three dimensional neural network in the brain. The aim of this study is to elucidate mechanisms underlying operation of neural networks from the viewpoint of the cerebral cortical inhibitory system using new functional imaging and photostimulation methods. If this simultaneous analysis of the neural network is advanced, it is expected that the results give us a new clue to understand how information from the external world is processed in the brain.

Title: Establishment of Neuroligin/Neurexin models for uncovering the etiology of neurodevelopmental disorders
Summary: Neuroligins and Neurexins are families of synaptic cell adhesion molecules considered to be involved in synaptic recognition and maturation. In this project, I will study the effects of their mutations found in the patients with autism on the synaptic function and behavior using mice that recapitulate those mutations in the genome. I also aim to evaluate and establish these mice as models of autism that can be used for autism research.

Title: Molecular basis underlying the formation and recognition of brain neural map
Summary: Neuronal synapse is the place to transmit, modulate and integrate the neuronal information. To enhance its processing capacity of neuronal information, neural network utilizes the spatial information of "the synaptic arrangements in the brain (neural map)".
The PRESTO research, by using Drosophila genetic methods, aims to elucidate the molecular basis underlying the formation and recognition of "Neural map", which is created by the interactions between dendrites and axons.

Title: Innovating optical sensing of transmembrane potentials
Summary: Cells generate electric field across plasma membranes. Rapid propagations of the membrane voltage changes though network of nerve cells are most presumably foundermental process underlying brain functions. This project focuses on innovative optical sensing of transmembrane potentials, utilizing recent advance in our understandings of protein-voltage as well as protein-photon interactions which occur in nanometer scales.

Title: Mechanisms for postnatal refinement of cerebellar circuits
Summary: The aim of this research is to elucidate the mechanisms for postnatal refinement of the cerebellar climbing fiber to Purkinje cell synapse. In adult cerebellum, most of Purkinje cells are innervated by a single climbing fiber. However, Purkinje cells are transiently innervated by multiple climbing fibers at the immature stage. Surplus climbing fibers are eventually eliminated during postnatal development, and the adult innervations pattern is attained by the end of third postnatal week in mice. This study will contribute to the understanding of the postnatal refinement of neuronal circuits in central nervous system.

Title: Neuronal network of the basal ganglia in motor and mental functions
Summary: The basal ganglia are the key neural substrates that control motor, cognitive and motivational functions, and their dysfunction leads to abnormalities such as Parkinson's disease, drug addiction and schizophrenia. I will address the regulatory mechanisms in the functions and dysfunctions in the basal ganglia network using reversible neurotransmission-blocking method and animal models of neurological and psychiatric diseases.

Title: Manipulation and imaging of neurogenesis in the adult mammalian retina
Summary: Recent studies have shown that adult mammalian retina can generate new neurons in response to acute retinal damages. Unlike lower vertebrates, however, mammals have only a limited capacity for retina self-repair. In this project, I plan to develop methods to enhance the neurogenic potential of retinal stem cells in the adult mouse retina by genetic manipulation. In addition, I plan to visualize neurogenesis in vivo in the adult mouse retina.

Title: Role of sleep in neuronal circuit reorganization
Summary: Sleep remains something of a biological mystery. Sleep has been implicated in an active role for learning and memory. However, it is difficult to understand the interaction between sleep and learning/memory because of complexities of both systems. The purpose of this study aims to find experimental evidence of neuronal circuit reorganization during sleep, using multi-neuron recording from visual cortex as a reduced model for sleep and memory.

Title: Brain research based on integrated analyses of molecular, electrophysiological and behavioral changes
Summary: Gene expression in neuronal cells is crucial for memory and learning. However, the relationships between electrophysiological or behavioral changes and the gene expression are unclear. In this study, we will observe the gene expression levels and electrophysiological and behavioral changes simultaneously by using transgenic mouse lines in which gene expression leads to the expression of fluorescent proteins in the activated neurons. We will analyze the relationships among them and reveal the mechanisms underlying memory and learning.

Title: Behavior contol by manipulating of the activity of the hypothalamic neural circuitry which involved in an instinct
Summary: The hypothalamic neurons are involved in the regulation of feeding and sleep/wakefulness behavior. However, little is known about the regulatory mechanism of these behaviors.This study reveals the neural mechanisms of sleep/wakefulness regulation by using transgenic animals which the light-activated proteins are expressed in the specific type of neurons in the hypothalamus.

Title: Mechanisms for the post-embryonic remodeling of the mechanosensory lateral line system
Summary: The lateral line system is composed of mechanosensory organs distributed over the body of fish. The number of mechanosensory organs increases during post-embryonic development, and the lateral-line nerve continues to develop throughout life. This study reveals molecular and cellular mechanisms regulating the post-embryonic remodeling of the lateral line system in zebrafish. These mechanisms underlie fundamental biological processes such as cell proliferation, migration, differentiation and regeneration. This study will offer applications to regenerative medicine for inner-ear diseases in humans, and provide novel insights into the development of diverse nervous system in vertebrate.