Department of Physiology（Physiology）

Our department first opened its doors with the arrival of the first professor Katsuo Seto in April 1978 as the First Department of Physiology. With the help of Assistant Professor Hideo Saito, Professor Seto made the department into an equally appealing place for both research and education. After Professor Seto became Vice President in May 1992, Professor Takashi Higuchi succeeded him as the second department chair in April 1993. With the departure of Professor Higuchi to University of Fukui Hospital in July 1997, Professor Hideto Kaba assumed position as the third department chair in December 1997. A course restructuring in April 2003 led to a name change to the Department of Integrative Physiology but later changed back to the original Department of Physiology in April 2006 with the Circulation Control Department (formerly known as Daini Physiology), changed to the subsequent Physiology Courses: Comprehensive Physiology and Circulation Control. With the retirement of Professor Kaba in April 2016, Masahiro Yamaguchi succeeded him as the fourth department chair, inheriting the research of Professor Kaba. The department researches memory, learning, links, emotions, neural plasticity, adult neurogenesis, and higher-level neural processes with a focus on olfaction.

The brain is a complex organ and has evolved to improve its responses to the environment of individual animals and thus increase the animal’s level of survivability. Studying how the individual animal learns of its changing environment and takes the appropriate action is an important approach in learning the true nature of the brain.

With a focus on the olfactory system, we study the brain’s sensory system (how an animal learns of their surrounding environment), behavioral system (how an animal makes its decisions) and plasticity mechanism (how an animal adapts to the changing environment). The olfactory system is a fundamental sense, affecting our emotions and feelings, and ultimately influencing our actions. By maximizing the potential ability of the olfactory system, we hope to uncover the brain’s plastic ability to make actions based on the changing environment and determine the underlying mechanisms involved including emotion, motivation and the link between individuals. We use a variety of research methods including electrophysiological examinations of freely-behaving animals and brain slices, brain imaging, optogenetics, and cellular and molecular-level analysis.

1. The elucidation of the neural mechanism behind emotional behavior and smell

The sense of smell is a sensory system directly coupled with sensory input but behavioral output is often driven by strong emotions and motivations. When attracted to a scent, behavior and motivation shifts to find the scent favorable and desire the scent whereas when avoiding a scent, behavior and motivation shifts to dislike and evade the scent. Such behaviors are newly learned from the individual’s experiences.

　

In our research, we are interested in identifying what area of the neural circuits synaptic plasticity occurs when encountering a new scent. By the electrophysiological recordings in various regions of the olfactory bulb and cortex of an active mouse, we examine how changes in information processing and interaction among these regions occur as a result of emotional behavior learning. We are attempting to understand the mechanism of neural plasticity that links sensory input to emotional behavior.

2. The elucidation of incorporation mechanisms of newly generated neurons

One of the most prominent features of olfaction is that new neurons are formed even after reaching adulthood (adult neurogenesis). Though the adult brain does not normally form new neurons, the olfactory bulb, the first relay of sensory processing, is constantly incorporating new neurons into its neural circuitry, contributing to a high level of plasticity within the olfactory system. From our research, we have determined that the incorporation of new neurons is a result of interactions between two synapses: input of smell from the periphery, and central input from the olfactory cortex of the upper central nervous system. Our goal is to uncover the cellular mechanism behind how two synaptic inputs come together and how the unification is controlled as well as uncovering the biological implications of the central synaptic input. We are currently using techniques such as virus-mediated cell labeling and functional molecular expression, and optogenetical control of synaptic input. Using this knowledge, we hope to contribute to the fields of neuronal regeneration and transplantation.

3. The elucidation of changes to the neural circuit accompanying pheromonal recognition memory

A higher level function of the brain, the mystery of learned behavior (and how the mechanism works) is an issue that has been a great point of interest for both neurobiologists and neuroscientists alike. In order to uncover the mysteries behind the neural mechanisms involved in learning memory, we use pheromonal recognition memory, taking advantage of copulatory stimulus in female mice when the memory of the male scent is imprinted. In addition, we have taken morphological and behavioral approaches to prove that this pheromonal recognition memory is aided by synaptic plasticity formed in the accessory olfactory bulb (at the first relay of the vomeronasal system).

　

We also aim to analyze the change in neural circuits from pheromonal recognition memory at a cellular level. Specifically, we focus on the synaptic interactions between mitral cells and granule cells, one of the main neural circuits within the accessory olfactory bulb. Through the use of electrophysiological techniques and Ca2+ imaging, we analyze how the presence or absence of pheromonal recognition memory affects the neural pathway. Furthermore, we are trying to determine the functional molecule (synthetic enzyme protein) involved in the transformation of these neural circuits.

4. The elucidation of individual (genealogical) recognition mechanism

An individual can produce a variety of chemical compounds and within these compounds are qualities, or markers, which can be used to identify the individual. In rodents, the volatile and non-volatile peptides secreted from one specimen are used in helping other species identify the breed, gender, reproductive condition, and genetic qualities of the individual in an informational code package of scent received via the sensory cells of the vomeronasal organ. There are only a few substances that have been determined to help animals identify each other such as the MHC class I peptide ligand and the Major Urinary Protein (MUP). In our research, we hope to uncover a new recognition substance involved in the breeding-recognition mechanism by using the lineage-specific pregnancy block (the Bruce effect) found in inbred mice with wild mice.

5. The elucidation of neural mechanisms which aid feeding behavior

Food is not only vital for life but is, at the same time, one of life’s greatest joys. It has been discovered that your eating habits in your early years will ultimately continue to affect your feeding behavior over your lifetime and that eating is not only a means of maintaining health in the elderly, but also has become an important part of daily life. Understanding the mechanisms behind feeding behavior will immensely contribute to the way in which we understand how to have healthy and fulfilling lives. From our research with mice, we have learned that feeding is heavily dependent on smell and that a greatly appetizing smell that makes one think “I want to eat it” will create motivation, activating a specific area within the olfactory tubercule (a subarea in the olfactory cortex). We will continue to research this region from the basics such as the construction of neural pathways, development, and plasticity resultant from feeding experience and widen our understanding as to how this affects humans in terms of functionality and feeding-related diseases.