Title: Understanding the neural mechanism and the development of postnatally acquired auditory communication.
Summary: Songbirds postnatally acquire an ability to communicate each other through vocal signals. For understanding the biological basis of the neural mechanism of auditory language comprehension, this study attempts to reveal the neural mechanism and the development of an ability of songbirds to discriminate the syntactical features in auditory information.

Title: Role of neuronal cilia in development and function of the central nervous system
Summary: Cilia are microtubule-based organelles that extend from basal bodies and form on the apical surface of cells. In this study, we will try to clarify ciliary functions in development and maintenance of the central nervous system. We will also study regulatory mechanisms of food intake activity through the hypothalamus cilia. These studies will contribute to clarify the pathogenesis of diseases cased by defects in ciliary function including neurodegenerative disease, obesity and diabetes.

Title: Experience dependent regulation of neural activity in brainstem auditory circuits
Summary: Neuronal activity contributes to development, maintenance and refinement of neural circuit. However, its underlying mechanisms are poorly understood. We recently found a novel plasticity that occurs at the axon initial segment, the site where neuronal activity arises. In this project, I will examine mechanisms and roles of this plasticity in a well-defined brainstem auditory circuit. The aim of this project is to understand molecular and cellular mechanisms on how neural curcuit function is achieved and maintained in an experience dependent manner.

Title: Learning-related plasticity of cortical microcircuits
Summary: Our behavior relies on harmonious activity of individual neurons. Local connections among neurons within a couple hundred micrometers, called microcircuits, are important units through which neurons generate their output from multiple inputs. However, little is known about the dynamics of microcircuits in behaving animals, especially during learning. In this proposal, we will reveal cellular and molecular mechanisms of learning-related plasticity of microcirtuits.

Title: Elucidating mechanisms that govern formation of functional neuronal circuit in the Drosophila visual system
Summary: The Drosophila visual center shares many important features of neurogenesis with mammalian brains: production of wide variety of neurons in accord with order of neuron production and formation of layer and columnar structures accompanying neuronal migrations. Additionally, powerful neurogenetic tools of Drosophila allow us high-resolution functional analyses of neuronal circuits by utilizing behavioral assays. Using the Drosophila visual system as a model, conserved mechanisms that govern formation of functional neuronal circuits will be elucidated.

Title: Analysis on left-right asymmetry in rodent brain.
Summary: It is well known that there is asymmetry in brain. For example, in most people, left hemisphere controls language, and 90% of people are right-handed. However, little is known about how the left-right asymmetry is established in brain. In this study, we investigate the mechanism that forms brain asymmetry, using novel genetically modified mice, which enable us to visualize left-right brain asymmetry. Furthermore, physiological significance of the brain asymmetry will be investigated using behavior tests.

Title: Uncovering Phosphorylation-Dependent Functional Modification Mechanisms in the Limbic Neural Circuits
Summary: When we change our emotional behavior in response to external stimuli, cell modifications are believed to occur that change the level of neuronal circuit activity. In order to understand these phospohorylation-dependent modification mechanisms as they relate to the regulation of emotional behavior, we intend to focus on the possible functions of a protein kinase, which has been shown to be highly expressed in a unique subset of nuclei in the limbic systems. Furthermore, we intend to develop new genetically modified mice that will enable us to manipulate local limbic circuitry at the molecular level.

Title: Neural Mechanisms Regulating the Internal Environment of the Brain
Summary: The sensory information can be processed variously according to the interanl environment of the brain such as mood and body conditions. These factors have been shown to be involved with the synaptic functions of biogenic amines and neuropeptides. The aim of this project is to understand how these neurotransmitters modulate the sensory processing and thus regulate the internal environment of the brain using Drosophila olfactory system as a model.

Title: Spatiotemporal analyses of signal transduction mechanisms controlling axon guidance
Summary: The formation of precise neuronal networks depends on the growth cone, a motile structure at the tip of elongating axons. The growth cone navigates the axon along the correct path by sensing a variety of extracellular guidance cues. In this study, I aim to elucidate the signal transduction mechanisms by which the growth cone integrates multiple extracellular guidance signals and translates them into correct guidance behaviors in vivo.

Title: Understanding of neural basis for biological clocks which control behavioral rhythms.
Summary: In mammals, the principal circadian pacemaker driving daily physiology and behavioral rhythms is located in the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. On the other hand, much shorter than 24 h rhythm has been observed in physiological functions, we call it an ultradian rhythm; however the neural basis of the ultradian rhythm remains to be elucidated. We will determine the neural circuits of this ultradian rhythm in the mammalian brain and will integrate the distinct timing of circadian and ultradian rhythms for better understanding of central nervous system.

Title: Molecular basis of the neural circuit controlling behavioral circadian rhythms
Summary: All animals need to generate and shape their behavior that suits their internal and external environments to survive and reproduce. Behavioral circadian rhythms offer an excellent substrate to study mechanisms underlying behavioral control, as they are robust, quantitative, and universal to most animals. However, despite a long history of the circadian rhythms research, the logic of the neural circuit controlling circadian behavior has been largely unknown. The objective of this project is to better understand the circadian circuit from the molecular to the system level in a model organism Drosophila.

Title: Examination of relationship between dendritic spines in the prefrontal cortex and behavioral phenotypes by using optogenetics
Summary: Prefrontal cortex (PFC) has been implicated in cognitive behaviors, and its disturbance is implicated in pathogenesis of mental disorders such as schizophrenia. Despite this significance, molecular mechanism(s) of PFC functions have been elusive. Here, I will utilize stereotaxic viral injection to manipulate schizophrenia-related genes in the PFC, and the injected rats will be subjected to longitudinal in vivo dendritic spine imaging and behavioral analyses. Furthermore, novel optogenetic tools, which can manipulate the plasticity of the dendritic spine, will be used to alter behaviors. By these two strategies, I will pursue the cause-effect relationship between the PFC spines and behavioral manifestations.

Title: Regulatory Mechanisms of Vascular Development Involved in Cytoarchitecture of Mammalian Cerebral Cortex
Summary: The aim of my reseach program is to understand cooperative role of vasculature development in neuronal development in the mammalian cerebral cortex. I postulate that the same cell-autonomous, regional and temporal patterning signals that regulate neural stem cells also regulate development of vascular　networks, and vice versa. In addition to providing insight into fundamental principles governing the biology of neural stem cells, discoveries made here may facilitate the directed manipulation of stem cell populations for therapeutic cell replacement strategies to repair the damaged or degenerating nervous system.