Structural and Functional Organization of the Nervous System

Brain contains many kinds of cells. The diverse cell populations make precise connections, and malformation of the brain results in psychiatric and neurological disorders. We use multidisciplinary technologies (i.e. immunohistochemistry, in utero electroporation, whole-cell patch-clamp and optical imaging) to elucidate the total landscape of the brain architecture and functions. We are investigating molecular and physiological basis of brain development, expression patterns of proteins in the brain, and cooperation among neuron, glia and blood vessels. We are also developing novel tools for optical imaging and histology for better understanding of the brain structure and functions.

Current projects include:

1. Expression patterns of bone morphogenic proteins (BMPs) in the adult brain. (Kohji Sato and Sumiko Mikawa)

BMP was first identified as a factor to induce ectopic bone formation. The functions of BMP have been intensely studied during early development. However, it has not been clear whether BMP and BMP-related proteins are expressed and work in the adult brain. We are investigating expression patterns of BMP and BMP-related proteins in the adult rat brains using immunohistochemistry.

2. Exploring novel guidance molecules and their functional significance in the brain formation and disorders. (Satoru Yamagishi)

Guidance of cells and axons to the right pathway is critical for brain formation and functions. We are studying an axon guidance molecule, FLRT2, and found that FLRT2 acts on both neurons and blood vessels (Yamagishi et al., 2011; Tai-Nagara et al., 2017). We are further analyzing neurovascular coupling with FLRT2.

We are also exploring novel guidance molecules. Recently, Netrin-5, a new protein of the Netrin family was identified, and its strong expression was observed in the neurogenic area in the adult brain (Yamagishi et al., 2015). We are now investigating the functions of Netrin-5 in adult neurogenesis and neuronal migration to the olfactory bulb and hippocampal dentate gyrus. In addition, we unexpectedly found that a BMP antagonist protein acts as a guidance molecule to astrocytes in vitro. Further analysis is in progress on functional significance of astrocytic navigation with this protein in recovery from brain damage in vivo.

3. From ion channels to neural circuits: physiological basis of neocortical development and function. (Yuki Bando)

Neurons express diverse types of ion channels, and orchestration of the ion channels shapes patterns of neural activity. However, the mechanisms are not totally understood how ion channels regulate neural computation at cellular and circuit levels in behaving animals. We use whole-cell patch-clamp, two-photon Ca²⁺ and voltage imaging to monitor electrical activity in subcellular compartments and population of neurons in vivo.

Neural activity regulates development and plasticity of the neural circuits. We are investigating how ion channels spatially and temporally shape neural activity, and how ion channels regulate transformation of extracellular signals to intracellular signals during development and learning. We use both physiological and histological methods to integrative understanding of activity-dependent formation and remodeling of the neural circuits.

Dysfunction of ion channels cause neurological and psychiatric disorders. Diseases caused by ion channel dysfunction are called "channelopathy". We are investigating how ion channel dysfunction affects neural circuit formation and computation at cellular and circuit levels.

New technologies strongly drive science. We are developing novel optical probes, especially genetically-encoded voltage indicators to monitor neuronal activity with subcellular resolution in behaving animals.

4. Mechanisms of atherosclerosis and aortic aneurysm development. (Takeshi Sasaki)

Abdominal aortic aneurysm (AAA) is a common disease among elderly individuals, which involves the progressive dilatation of the abdominal aorta as a consequence of degeneration. Currently, surgical repair is the only available method of treatment since lack of knowledge regarding the pathogenesis of AAA has hindered the development of suitable medical treatments. In addition, arteriosclerosis, which is thought to be the basis for aneurysm formation, is not fully understood.

We have published various animal models such as thrombus formation, atherosclerotic plaque disruption, and AAA formation and disruption, and we have been conducting continuous researches using these models. In these studies, it has been clarified that proteases such as matrix metalloproteinases (MMPs) and cathepsins, and inflammatory cells which secrete above-mentioned proteases are deeply involved in these diseases. Currently, we investigate mechanisms by which these inflammatory cells are activated and release proteases, focusing on adipocyte and adipocytokines.

5. Histological analysis of biological molecules and development of histological methods. (Takeshi Sasaki)

Histological analysis is an important and essential method in the fields of medical and life science. We aim to devise and develop solutions and new methods for some problems, especially in the methods of histological and immunohistological staining. We have published several papers and received a study group award in the last 10 years of research on this project.

6. Improvement educational methods and environment in anatomy. (Takeshi Sasaki)

Anatomical education in medical and dental faculties, especially the gross anatomy, is essential course. Recently, the gross anatomy courses for co-medical students are held for more than 10 external educational institutions and medical associations in Hamamatsu university school of medicine. In this course, we are working on the preparation and improvement of educational specimens, materials and methods which will deepen students' understanding. Furthermore, in the gross anatomy course, the working environment such as the formaldehyde concentration in the room often becomes a problem. Therefore, we are constantly improving the working environment of an