Members of Publicly Invited Research

• A01 Publicly Invited Research
• A02 Publicly Invited Research
• A03 Publicly Invited Research

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  Natsuko HITORA‐IMAMURA

  Graduate School of Pharmaceutical Sciences, Hokkaido University

  Research projects

  Elucidation of neuronal population mechanisms underlying willdynamics

  Research projects
  Elucidation of neuronal population mechanisms underlying willdynamics
  
  Research abstract
  Animals decide whether they should do something based on the balance between positive and negative emotions that promote or prevent behavior. The purpose of this study is to elucidate a neuronal mechanism of willdynamics by studying how neuronal activities regulating positive and negative emotions are switched depending on the situation and how they change animal's behavior.
  1, We are going to elucidate neuronal activities that control behavior in a conflict task in which animals are given both positive and negative stimuli.
  2, We are going to elucidate a causal relationship between neuronal activity and behavior.
  3, We will improve “motivational imbalance” by manipulation of neuronal activities in a rodent model of depression.
  

• 

  Michael LAZARUS

  Principal Investigator, International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba

  Research projects

  Willdynamics of REM sleep and appetite

  Research projects
  Willdynamics of REM sleep and appetite
  
  Research abstract
  It is widely accepted that sleep disruption affects metabolism and energy balance, but the neuronal mechanisms linking sleep disruption and obesity are poorly defined. Recent work from the WPI-IIIS Lazarus lab suggests a role of neurons in the medial prefrontal cortex (mPFC) in linking REM sleep to the control of appetite for highly palatable food (HPF; McEown K, et al. eLife 2016;5:e20269). Moreover, the Lazarus lab discovered that REM sleep is suppressed by activation dopaminergic or GABAergic ventral midbrain/pons (VMP) neurons (Oishi Y, et al., Brain Struc Func, 2017; 222:2907-2915; Takata Y, et al., J Neurosci, 2018;38:10080–10092). These neurons, however, are known to be active during REM sleep, suggesting that these neurons may have other functions during REM sleep. Therefore, the WPI-IIIS Lazarus lab is currently investigating the role of a VMP/mPFC circuit for healthy dietary behavior during REM sleep.

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  Takaaki OZAWA

  Osaka University

  Research projects

  Dopamine dynamics controlling sustained reward seeking

  Research projects
  Dopamine dynamics controlling sustained reward seeking
  
  Research abstract
  Dopaminergic system is a key regulator in control of motivated behavior. However, its dynamics and functional role during sustained reward seeking remain largely unknown. We will address this question by taking advantage of recently developed dopamine sensor and optogenetics.

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  Katsuyasu SAKURAI

  University of Tsukuba, International Institute for Integrative Sleep Medicine (WPI-IIIS)

  Research projects

  Capture the orgasm

  Research projects
  Capture the orgasm
  
  Research abstract
  The biological purpose of sex is to transfer the genes to the next generation. In other words, the desire of sex is the desire for future life. In my view, the desire for sex may be fulfilled by achieving the “orgasm”, hence, the central question is: what is the neural representation of orgasm in the brain. In case of the male mouse, sex consists of a series of sequential behaviors: female recognition, chasing, mounting, intromission and ejaculation as the climax. It is often thought that ejaculation triggers orgasm or vice versa. Thus, we are in the process of identifying the neural ensemble that encodes orgasm using histological and imaging techniques. Afterwards, we will investigate the causality between the neural activity of the specific neural population and ejaculation/orgasm.

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  Akihiro YAMANAKA

  Research Institute of Environmental Medicine, Nagoya University

  Research projects

  Identification of factors to regulate noradrenaline neurons in the locus coeruleus and its physiological factor

  Research projects
  Identification of factors to regulate noradrenaline neurons in the locus coeruleus and its physiological factor
  
  Research abstract
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  Hiroyuki MIZOGUCHI

  Research Center for Next-Generation Drug Development, Research Institute of Environmental Medicine, Nagoya University

  Research projects

  Activities of orexin neurons in reward-motivated behaviors under conditions of uncertainty

  Research projects
  Activities of orexin neurons in reward-motivated behaviors under conditions of uncertainty
  
  Research abstract
  Life is a series of choices under complex and uncertain conditions. Willpower is necessary for optimal performance and choice in daily life activities, and weakened willpower may induce errors in choice strategy and judgement. Conversely, a strong willpower enables higher brain functions, including judgment, prediction, and decision-making, leading to improved performance (motivated behavior). The best way to elicit high performance is to strengthen a person’s willpower, or enable them to exercise willpower when needed. However, is strong willpower sufficient to improve performance? Everybody is familiar with cases in which someone tries very hard but still does not succeed—in other words, it is possible that willpower can actually lead to impaired performance. Therefore, it is important to refine willpower and place it under the control of higher brain functions, such as in-the-moment judgments, prediction, and decision-making.
  Orexin neurons regulate physiological functions, including not only energy homeostasis and wakefulness, but also motivated behaviors. These neurons play important roles in linking metabolic requirements to motivated behaviors via the dopaminergic system. Recently, we found that orexin neurons modulate positive reward prediction, reward motivation, and probability learning to obtain rewards under conditions of uncertainty. Moreover, we found that orexin neurons also modulate motivational value to reward using a computational approach. Therefore, we believe that activated orexin neurons affect motivational processes, and may alter strategy in reward-based choice behavior, potentially leading to actions that fail to yield rewards and detect changes in reinforcement probability. However, we do not yet know whether the activities of the orexinergic pathway are actually changed in motivated behavior.
  In this research, we measured the activities of orexin neurons in reward motivation and analyzed the changes in motivated behaviors when orexin neurons were manipulated using optogenetic approaches.
  
  

• 

  Hiroyuki WATANABE

  Graduate School of Pharmaceutical Sciences, Kyoto University

  Research projects

  Development of molecular imaging probes for the elucidation of willpower

  Research projects
  Development of molecular imaging probes for the elucidation of willpower
  
  Research abstract
  Orexins exert multiple functions, particularly in areas related to energy homeostasis, sleep/arousal, and brain reward mechanisms, via signaling derived from orexin receptors (OXR). Molecular imaging techniques are attractive tools for the elucidation of biological functions in living subjects. The advantages of positron emission tomography (PET), which is one of the nuclear medicine imaging techniques, include high sensitivity, noninvasive and functional imaging. However, useful PET probes for selective imaging of orexin receptor have not been reported. In this study, we develop novel PET imaging probes targeting OXR. In addition, we carry out PET studies using some model mice to elucidate the relationship between orexin system and nerutransmitters related with “will-power”

• 

  Masaaki OGAWA

  Research projects

  Neural basis for driving willpower to overcome reward uncertainty

  Research projects
  Neural basis for driving willpower to overcome reward uncertainty
  
  Research abstract
  Although we often boost willpower to overcome negative reward prediction errors associated with uncertain rewards, the neural basis is not well understood. In this research, we will aim to clarify the neural basis of this willpower, focusing on the roles of neural circuits involving midbrain dopamine neurons, using a sophisticated behavioral model that we have recently established in rats and optogenetic techniques to monitor and manipulate the neural activities.

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  Kaoru SEIRIKI

  Research projects

  Whole-brain imaging analysis of neuronal networks involved in adaptation and maladaptation to stress

  Research projects
  Whole-brain imaging analysis of neuronal networks involved in adaptation and maladaptation to stress
  
  Research abstract
  Stress responses can be both adaptive and maladaptive processes according to stress intensity. In particular, severe stress is a major risk factor for depression and posttraumatic stress disorder and disrupts brain functions including motivation and emotion. To understand the difference of neuronal mechanisms underlying adaptive and maladaptive stress responses, we will determine the brain regions and circuits involved in these responses by whole-brain mapping of neuronal activation elicited by single or multiple social defeat stress exposure in mice.

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  Hideyuki MATSUMOTO

  Department of Physiology, Osaka City University Graduate School of Medicine

  Research projects

  Context-dependent dopamine signaling in willpower regulation

  Research projects
  Context-dependent dopamine signaling in willpower regulation
  
  Research abstract
  External reward exerts powerful influence on our willpower. Dopamine is thought to be one of the key molecules to link external reward in natural environments to willpower, but the neuronal circuit mechanisms still remain elusive. In this project, combining large-scale multi single neuron recordings and optogenetics, we will investigate the activity patterns of dopamine neurons to generate willpower for overcoming difficulties toward their goal. By identifying the distinct neuronal circuits responsible for specific aspects of willpower, we will contribute to the targeted and effective treatments for willpower deficits.

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  Ayumu INUTSUKA

  Department of Physiology, Jichi Medical University

  Research projects

  Neural mechanisms of willpower to seek for social interaction

  Research projects
  Neural mechanisms of willpower to seek for social interaction
  
  Research abstract
  Willpower is a key element for surviving the competitive society. It affects individual health and contributes to social productivity. Social defeat stress induces depression-like behavioral changes including social avoidance. However, the neural mechanisms underlying social avoidance are not fully understood. Using in vivo recording of neural activities in free-moving mice or rats, we aim to reveal the neural mechanisms for regulating the willdynamics for social interaction. Oxytocin neurons innervate several brain regions such as the prefrontal cortex and the amygdala. We analyze the role of the oxytocin system in social avoidance, using retrograde/anterograde infection of viral vectors and other genetic tools.

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  Kenji TANAKA

  Department of Neuropsychiatry, Keio University School of Medicine

  Research projects

  Neural substrate for goal-directed action sustainment.

  Research projects
  Neural substrate for goal-directed action sustainment.
  
  Research abstract
  The ability to sustain goal-directed action is essential for success in many domains, but little is known about the corresponding neural substrates. In this project, we aim to address the role of the ventral hippocampus on goal-directed action sustainment.

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  Junya HIROKAWA

  Research projects

  Network mechanism for maintaining willpower by sustained neuronal activity in Orbitofrontal cortex

  Research projects
  Network mechanism for maintaining willpower by sustained neuronal activity in Orbitofrontal cortex
  
  Research abstract
  In order to suppress impulsive behavior, one must keep in mind his goal to resist the opposing temptation. When the power to sustain the thought is weaken, one yields to his impulses. This study investigates whether the willpower is causally related to the “sustained neuronal activity”, which is often observed in specific neuronal population in prefrontal cortex. We train rats to conduct a decision making task that requires them to make choices between “big reward with long delay” and “small reward with short delay”. By selectively manipulating the persistent activity of specific neuronal population in orbitofrontal cortex, we will determine whether the sustained activity is necessary for suppressing impulsive decision making.

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  Akira UEMATSU

  The University of Tokyo

  Research projects

  Prefrontal noradrenaline modulation in behavioral flexibility

  Research projects
  Prefrontal noradrenaline modulation in behavioral flexibility
  
  Research abstract
  Optimal noradrenaline level is important in prefrontal cortex for driving behavioral flexibility. Recently, we showed that optogenetic excitation of noradrenaline input to the prefrontal cortex (PFC) reduces fear extinction through a1 adrenergic receptor. However, it is not clear how PFC neural activity is affected by noradrenaline level. In this study, we aim to elucidate this question by using optogenetic and in-vivo imaging approaches.

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  Hiroshi YAMADA

  University of Tsukuba

  Research projects

  Role of front-striatal network in motivational control of actions

  Research projects
  Role of front-striatal network in motivational control of actions
  
  Research abstract
  Any kinds of our activities needs a willingness to do it, linking motivation to behavior based on rewards. I examine whether and how the front-striatal network play a role in motivational control of actions based on rewards by using monkeys who make decision makings similar to humans. The examination of behavioral regulation mechanisms to naturalistic rewards allow us to understand abnormal states of the brain, known as addictive behavior and maybe depression.

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  Keizo TAKAO

  Life Science Research Center, University of Toyama

  Research projects

  Development of animal model of breathing method and the application for willdynamics

  Research projects
  Development of animal model of breathing method and the application for willdynamics
  
  Research abstract
  A slow and deep breathing is an essential part of traditional meditation and discipline method in the Orient, which can enhance a willpower. In this research project, we will develop an animal model of the breathing method. Using this model, we will be able to elucidate the biological significance of breathing method in the regulation of a willpower. Artificial control of spontaneous breathing in an awake animal has been difficult, however, we utilize an innate preference of mice for environments and a real-time feedback system to develop the training system of breathing. This new animal model of breathing method will enable us to clarify neural mechanisms of the traditional mental training method that have been considered as a mystery in the East.

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  Toshiyasu SASAOKA

  Graduate School of Medicine and Pharmaceutical Sciences
  University of Toyama

  Research projects

  Strengthen of willdynamics via the olfactory system to prevent depression and diabetes

  Research projects
  Strengthen of willdynamics via the olfactory system to prevent depression and diabetes
  
  Research abstract
  Depression and type 2 diabetes are increasing in the modern society where lifestyles and social structures are changing rapidly. Since the onset and development of these disorders are closely linked, it is highly possible that strengthen the stress adaptability could prevent the vicious circle of the diseases. In the present study, I focus on the olfactory system that is directly linked to emotion and instinctive behavior. I clarify that olfactory system integrates the central functions of reward, arousal, and energy supply for maintenance of mental (brain) and metabolic (visceral) functions. Strengthen of willdynamics via stimulation of the olfactory system would be a novel intervention to prevent depression and diabetes.

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  Toshihisa OHTSUKA

  Graduate School of Medicine/Faculty of Medicine, University of Yamanashi
  

  Research projects

  Understanding of WILLDYNAMICS by regulation of synaptic transmission and functional relationship between central and peripheral systems.

  Research projects
  Understanding of WILLDYNAMICS by regulation of synaptic transmission and functional relationship between central and peripheral systems.
  
  Research abstract
  It has been suggested that the connection between the central nervous system and peripheral organs is important for the control of will power, but the underlying mechanism has hardly been elucidated. In this study, we focus on the presynaptic molecules CAST/ELKS in the central nervous system, and analyze the functional linkage between peripheral organs such as adrenal medulla and pancreas and the central nervous system, in the context of the release mechanism of transmitters and its failure. The obtained results have the potential to bring about new strategies targeting "presynaptic molecular mechanisms" in establishing the onset mechanism and treatment of endocrine diseases and neuropsychiatric diseases. Furthermore, in the future, we aim to contribute greatly to the understanding of mental and neurological diseases such as depression and withdrawal, and to widely contribute to the promotion of public health and welfare.

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  Eiji SHIGETOMI

  Department of Neuropharmacology, Graduate School of Medicine, University of Yamanashi

  Research projects

  Astrocytic mechanisms in motivation

  Research projects
  Astrocytic mechanisms in motivation
  
  Research abstract
  Astrocyte, one of glial cells in the brain, is severely impaired in patients with depression, who lack “motivation”. Astrocytic Ca2+ signal and its downstream pathways such as secretion of neuroactive substances are downregulated in experimental animals which show depression-like behaviors. We aim to enhance “motivation” in mice by manipulating astrocytic Ca2+ signals selectively and to gain an insight into role of astrocytes in behaviors driven by “motivation”.

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  Shiho KITAOKA

  Kobe University

  Research projects

  Elucidating whether and how hematocytes hamper will power.

  Research projects
  Elucidating whether and how hematocytes hamper will power.
  
  Research abstract
  Social and environmental stress activates sympathetic nerve and hypothalamus-pituitary-adrenal axis (HPA axis) as a survival mechanism. On the other hand, excess and prolonged stress, which is a risk factor for mental illnesses, declines cognitive function and induces emotional changes. We found that repeated stress activates microglia, leading to inflammation-like response in the brain. Recently, it has been reported that activation of sympathetic nerve and HPA axis induces inflammation in peripheral organs. In this research, we will examine the role of hematocytes in inflammation-like response in the brain and identify the biomarker which indicates “stress level”.

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  Shozo JINNO

  Kyushu University

  Research projects

  Analysis of cocaine addiction from the view point of adult hippocampal neurogenesis

  Research projects
  Analysis of cocaine addiction from the view point of adult hippocampal neurogenesis
  
  Research abstract
  For a long time, the major target of addiction research is the reward system, consisting of dopaminergic pathways from the ventral tegmental area to the nucleus accumbens. However, more recently, the adult neurogenesis in the hippocampus has become the focus of attention, because several reports have shown its impairment in animal models for drug addiction. In this project, we aim to understand the potential involvement of the adult hippocampal neurogenesis in the pathophysiology of drug addiction using the mouse model of cocaine-induced conditioned place preference. We will make full use of the resources developed in our lab for the microstructural and electrophysiological analyses. For further understanding the implication of adult hippocampal neurogenesis in drug addiction, we will perform a series of behavioral analyses. Our objective is to advance the basic research for new therapy to treat drug addiction cooperating with other investigators in this research area.

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  Nobuyuki SAKAYORI

  Department of Physiology and Oral Physiology, Graduate School of Biomedical and Health Sciences, Hiroshima University

  Research projects

  Lipid molecules to produce willpower and its dysregulation by modern diets

  Research projects
  Lipid molecules to produce willpower and its dysregulation by modern diets
  
  Research abstract
  Increase in the number of obese patients is the important health problem in the modern society. Dopamine in the brain is one of neurotransmitters that regulate feeding behavior; increased amount of dopamine in the nucleus accumbens reinforces motivational aspects of feeding. Identification of environmental factors that regulate dopaminergic neurons and feeding behavior is the urgent social need. In this study, we focus on intake of lipids, which has been qualitatively and quantitatively changed during the last several decades, and analyze the impact of modern lipid diets on motivation to feed.

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  Rui NOUCHI

  Frontier Research Institute for Interdisciplinary Science (FRIS), Tohoku University
  

  Research projects

  Acute benefits of cognitive, exercise, and nutrition methods on a human performance.

  Research projects
  Acute benefits of cognitive, exercise, and nutrition methods on a human performance.
  
  Research abstract
  In an exam and a match, we want to show the best performance. The performance would be changed by our mental states such as a concentration, motivation or mood. This project aims to investigate whether a single cognitive, exercise, and nutrition intervention can improve a human performance. We select the brain training, the combination exercise, and the protein intakes as the single intervention. Our outcome measures are performances of everyday behaviors and cognitive functions. We believe that these single interventions may briefly enhance our performance.

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  Katsuyuki KANEDA

  Kanazawa University

  Research projects

  Neural mechanisms underlying the formation and maintenance of motivation for exercise

  Research projects
  Neural mechanisms underlying the formation and maintenance of motivation for exercise
  
  Research abstract
  Exercise improves our health and brain function. In this study, by focusing on the characteristic feature of mice to run on running wheels voluntarily, we try to elucidate the neural mechanisms underlying the formation and maintenance of motivation for exercise at the cellular, synaptic and behavioral levels. Specifically, we investigate which neuronal types in the nucleus accumbens (NAc) and dorsal striatum (DSt) play a role for the maintenance of exercise motivation and what neuroplasticity induced in NAc and/or DSt neurons contributes to the formation of exercise motivation.