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 activity underlying dynamic equilibrium of positive and negative emotions

  Research projects
  Elucidation of neuronal activity underlying dynamic equilibrium of positive and negative emotions
  
  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 circuit mechanism of willdinamics by studying how neuronal circuit 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 circuit activities that control behavior in a conflict task in which animals are given both positive and negative emotions using multi-site fiber photometry.
  2, We are going to elucidate a causal relationship between the neuronal circuit activities and the behavior using optogenetics.

• 

  Michael LAZARUS

  International Institute for Integrative Sleep Medicine, University of Tsukuba
  

  Research projects

  Pioneering a New Dynamics of Fear and Will, Leveraging a Novel Mouse Mutant with Unusual Fear Responses.

  Research projects
  Pioneering a New Dynamics of Fear and Will, Leveraging a Novel Mouse Mutant with Unusual Fear Responses.
  
  Research abstract
  In humans, REM sleep loss adversely affects dietary behavior which may lead to weight gain. For example, REM sleep loss in humans enhances the desire to consume food and increases food consumption (Gonnissen H.K.J., et al. Br J Nutr 2013, p. 748). Recent work from our lab suggests a role of neurons in the medial prefrontal cortex (mPFC) in linking REM sleep loss to the desire for food containing high levels of calories from sugar and fat, i.e., junk food (McEown K., et al. eLife, 2016;5:e20269). It remains, however, an open question whether highly palatable foods consumption is causally linked to REM sleep. We aim to elucidate by using chemogenetic methods and in-vivo imaging whether the activity of mPFC neurons that mediate preference for sucrose-rich diet is controlled by REM sleep-regulating pontine cholinergic neurons or wake-promoting midbrain dopamine neurons. This research may reveal a role of REM sleep in promoting 「Willpower」 to reject unhealthy dietary behavior. Obesity and closely associated diseases, including diabetes and cardiovascular disease, are on the rise. The understanding of the underlying brain mechanisms of how sleep loss affects metabolism and energy balance may lead to new strategies to prevent lifestyle diseases.

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  Qinghua LIU

  International Institute for Integrative Sleep Medicine, University of Tsukuba

  Research projects

  Pioneering a New Dynamics of Fear and Will, Leveraging a Novel Mouse Mutant with Unusual Fear Responses.

  Research projects
  Pioneering a New Dynamics of Fear and Will, Leveraging a Novel Mouse Mutant with Unusual Fear Responses.
  
  Research abstract
  High will-power is essential to overcome difficulties and live a creative and productive life, and “Fear” is one of the factors that antagonize the power. While the fear is an indispensable emotion to avoid danger, too much fear induces a thought stopping and failure in work, later it allegedly causes series of anxiety disorders. However, since the molecular mechanisms underlying the disorders or fear emotion itself are unclear, how the relationship between fear and will-power is represented in the aspect of neuroscience is still unknown.
  As we established a mouse mutant family that showed excessive fear responses through a novel forward genetic screen based on innate fear responses, we aim to develop a proof-of-concept revealing the antagonistic relationship between fear and will-power through identifying detailed mechanisms of will-power regulation, in combination with different approaches in neuroscience, behavioral study, and molecular biology.
  

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  Hiroyuki MIZOGUCHI

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

  Research projects

  Motivational neural circuitry based on manipulation of the orexin system: A novel system for investigating Willdynamics

  Research projects
  Motivational neural circuitry based on manipulation of the orexin system: A novel system for investigating Willdynamics
  
  Research abstract
  Willpower is necessary for optimal performance in daily life activities, and deficits in willpower may be related to the development of mood disorders through chronic stress on the body. Therefore, strengthening willpower provides better ways to survive in a stressful society. In basic research, willpower can be assessed by motivated behaviors aimed at receiving rewards. A better understanding of the neural mechanisms underlying motivated behaviors would provide insights into the ways that willpower can be developed.
  Orexin neurons regulate physiological functions, including not only energy homeostasis and wakefulness, but also motivated behaviors. These neurons seem to play important roles in linking metabolic need to motivated behaviors via the dopaminergic system. Recently, we developed a rat model that expresses the Cre recombinase specifically in orexin neurons. This model is useful for investigating the neural circuits underlying motivated behaviors. Moreover, we established the gambling test for assessing reward motivation under conditions of uncertainty, as well as a touch-screen system for assessing reward sensitivity and craving.
  We examine the roles of orexin neurons in reward motivation and analyze the changes in motivated behaviors when orexin neurons are manipulated using pharmacogenetic and optogenetic approaches.
  

• 

  Nobuhito ABE

  Kokoro Research Center, Kyoto University

  Research projects

  Neural correlates of willpower for regulation and facilitation of deceptive behavior

  Research projects
  Neural correlates of willpower for regulation and facilitation of deceptive behavior
  
  Research abstract
  The force of will is required in various situations, but its importance is very high in terms of controlling acts of dishonesty. For example, if one can benefit by telling lies, curbing the urge to tell lies would require the exercise of deliberate, calculated control, mainly by force of will, depending on the function of the prefrontal cortex. In this case, the target of control by the prefrontal cortex is considered to be the activity of the limbic system involved in the processing of emotional or reward information. Although both the mechanism of action control by the prefrontal cortex and motivation emergence by the limbic system are drives for the development of will, the relationship between the two neural systems within the context of moral decision making is still unknown. In this research, we aim to elucidate the cognitive and neurobiological correlates of willpower that are associated with regulation and facilitation of dishonesty by using web surveys and a cognitive neuroscience approach.

• 

  Hiroyuki WATANABE

  Graduate School of Pharmaceutical Sciences, Kyoto University

  Research projects

  Development of molecular imaging probes for the elucidation of orexin system

  Research projects
  Development of molecular imaging probes for the elucidation of orexin system
  
  Research abstract
  The orexin system, composed of two G-protein coupled receptors, orexins 1 and 2, and two neuropeptide agonists, orexins A and B, affects not only the regulation of wakefulness and food intake but also the level of nerutransmitters such as serotonin, dopamine, and noradrenalin. However, the function of orexin system has not completely elucidated. Molecular imaging is an excellent tool for the elucidation of biological processes. Especially, positron emission tomography (PET) shows higher sensitivity and quantification, but useful PET probes for selective imaging of orexin receptor have not been reported. In this study, we develop novel PET imaging probes targeting orexin 1 and orexin 2 receptor. In addition, we carry out PET studies of orexin and norepinefrin transporter imaging probes using some model mice to elucidate the relationship between orexin system and nerutransmitters related with “will-power”.

• 

  Katsuki NAKAMURA

  Primate Research Institute, Kyoto Unviersity

  Research projects

  Role of dopamine receptors on motivation to learn in primates

  Research projects
  Role of dopamine receptors on motivation to learn in primates
  
  Research abstract
  The aim of this study is to elucidate the role of dopamine D1, D2, and D3 receptor systems in motivation of learning in nonhuman primates (common marmosets). Firstly, we will develop a behavioral task to evaluate motivation of learning in marmosets. Secondly, we will selectively decrease dopamine D1, D2, or D3 receptor mRNA expression levels in the marmoset basal ganglia using shRNA knockdown techniques, and will examine the role of each receptor system in motivation of learning in marmotsets.

• 

  Ayumu INUTSUKA

  Department of Physiology, Jichi Medical University

  Research projects

  Willdynamics analysis using fiber photometry

  Research projects
  Willdynamics analysis using fiber photometry
  
  Research abstract
  Willpower is a key element for surviving the competetive society. It affects individulal health and contributes to the social productivity. Social defeat stress induces depression-like physiological changes and behaviors including social avoidance. While social interactions have ameliorating effects on stress, social isolation induces stress responses. Epidemiological studies have also shown that people with smaller social support network have higher mortality. However, the neural mechanism underling social avoidance is still not well understood. Using fiber photometry system, we aim to reveal the neural mechanism for regulation of the willdynamics in free-moving mice and rats. Oxytocin neurons innervate several brain regions such as the prefrontal cortex and the amygdala that are involved in social avoidance. 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 basis of active avoidance

  Research projects
  Neural basis of active avoidance
  
  Research abstract
  The motivated behavior can be classified by the nature of effort: the effort to get positive things (i.e. reward) and the effort to avoid expected negative outcome or escape concurrent distress. Food-incentive approach behaviors in animals are frequently used to address neural substrates of former motivated behaviors, however, the behavioral task for addressing latter motivation is lacking.Here we will establish a behavioral task to quantify the active avoidance in mice. We will next determine which cell type encodes active avoidance and address how the corresponding cell type behaves under the stressful condition.

• 

  Takayuki HOSOKAWA

  Division of Systems Neuroscience, Tohoku University Graduate School of Life Sciences

  Research projects

  Prefrontal neural activity related to the willpower of perseverance

  Research projects
  Prefrontal neural activity related to the willpower of perseverance
  
  Research abstract
  To investigate the neural mechanisms underlying perseverance (i.e., the characteristic traits that one continues trying to do something even thouth it is difficult), we will train Japanese monkeys in a “contest of strength”, where the monkeys apply force on the lever to win the contest. By applying force on the lever, a cursor on the PC monitor moves in the direction that the force is applied (forward or backward). We will quantify the perseverance of the monkeys by observing whether they would keep applying force even in a disadvantage situation (a situation that they are likely to lose the contest). To investigate which brain areas are responsible for the perseverance, we will deliver low-frequency repetitive transcranial magnetic stimulation (rTMS), which suppresses the function of the stimulated brain area, on various areas of the prefrontal cortex. Furthermore, we will record neural activity of the prefrontal cortex using implanted metal electrodes or ECoG electrodes. Through these experiments, we aim to elucidate the neural mechanisms underlying the willpower of perseverance.

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  Yoko IRUKAYAMA-TOMOBE

  International Institute for Integrative Sleep Medicine, University of Tsukuba

  Research projects

  Elucidation about roles of orexin receptor agonists on the immobility and lethargy in inflammatory model mice and approaches to new drug discovery

  Research projects
  Elucidation about roles of orexin receptor agonists on the immobility and lethargy in inflammatory model mice and approaches to new drug discovery
  
  Research abstract
  Although, it is considered that patients in the ICU who start exercise therapy early can leave from bed earlier (Schweikert et al., Lancet, 2009), many patients fall into specific mental states and find it extremely difficult to have the motivation and will for activities. Therefore, it is necessary to elucidate the internal and external environmental factors that promote motivation. Orexins are hypothalamic neuropeptides that play a highly important part in the regulation of wakefulness and have important roles in reward, hedonia, and motivation (Sakurai et al. Nat. Rev. Neurosci., 2012). We recently discovered a potent non-peptidic OX2R agonist, YNT-185 through a lead optimaization process. YNT-185 promoted recovery from LPS-induced immobility in mice. In this study, we aim to improve the motivation of patients with fatigue / immobility caused by inflammation such as infectious diseases and postoperative invasion. We plan to investigate roles of orexin on recovery and motivation in LPS-induced inflammatory model mice using new orexin receptor agonists, DREADD, and ontogenetic intervention.

• 

  Tsutomu SASAKI

  Lab for Metabolic Signaling, Institute for Molecular and Cellular Regulation, Gunma University

  Research projects

  Elucidating the role of brain SIRT1, an integrator of external and internal environment, in regulating will and motivation.

  Research projects
  Elucidating the role of brain SIRT1, an integrator of external and internal environment, in regulating will and motivation.
  
  Research abstract
  Recognizing the reward value and motivation to persue the reward are necessary for the expression of willpower. Both external information from social environments and internal information from the body influences the will power, yet how these information are integrated in the brain remain elusive.
  I have elucidated that SIRT1 in the brain improves sensitivity to internal information conveyed by hormones and that SIRT1 positively regulates oxytocin, the hormone which improves resilience upon social stress.
  
  In this project, I propose that brain SIRT1 regulates the willpower by integrating social and internal information, and regulates stress resilience. SIRT1 in the brain may function as a missing link between these internal/external information and brain function that regulates mind. I will test the hypothesis using genetically-modified mice and behavioral experiments in this project.
  

• 

  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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  Tomoyuki FURUYASHIKI

  Division of Pharmacology, Graduate School of Medicine, Kobe University

  Research projects

  Roles of neurite outgrowth-regulating molecules in the medial prefrontal cortex for stress resilience and their implications for lifestyle habits

  Research projects
  Roles of neurite outgrowth-regulating molecules in the medial prefrontal cortex for stress resilience and their implications for lifestyle habits
  
  Research abstract
  Various environmental factors, such as social and environmental stressors and lifestyle habits, affect our cognitive and emotional functions. Some enviromental factors may promote mental health, whereas others may promote mental illnesses. However, objective methods and criteria to predict which environmental factors promote our mental health have not been established. Using social defeat stress in mice, we found that brief stress exposure induces dendritic outgrowth of excitatory neurons in the medial prefrontal cortex (mPFC) and promotes stress resilience. In this research proposal, we will elucidate roles and actions of neurite outgrowth-regulating molecules in mPFC for stress resilience as well as the control of their gene expression. We will also examine the effects of dietary intake and sleep on dendritic morphology of mPFC neurons and stress resilience in mice. In addition, we will examine the relationship between lifestyle habits and stress-coping capacity in healthy human volunteers. Therefore, we aim to connect the findings about neural mechanisms underlying stress resilience in basic neuroscience to mental health promotion in our society.

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  Nobuyuki SAKAYORI

  Department of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University
  

  Research projects

  Congenital impairment in the control of feeding motivation caused by modern lipid diets

  Research projects
  Congenital impairment in the control of feeding motivation caused by modern lipid 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 the master neurotransmitters that regulate feeding behavior; increased amount of dopamine in the nucleus accumbens of the midbrain reinforces motivational aspects of feeding. Identification of environmental factors that regulate development and/or activity of 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. We further evaluate the functional shift of brain neural circuitry that underlies motivational components of feeding. This study will develop novel methods to prevent obesity with respect to lipid nutrition.
  

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  Mayumi NISHI

  Nara Medical University

  Research projects

  Neural mechanism of will control by a newly identified mouse hypothalamic area PeFAH

  Research projects
  Neural mechanism of will control by a newly identified mouse hypothalamic area PeFAH
  
  Research abstract
  The perifornical area of the anterior hypothalamus (PeFAH) is a hypothalamic area that we recently identified in the mouse brain, which locates between the fornix and paraventricular nucleus of the hypothalamus on the dorsal part of anterior hypothalamus. This area was clearly stained with WFA lectin-positive perineuronal nets. Our previous study has revealed that the PeFAH includes urocortin 3 (Ucn3) and enkephalin (Enk) co-expressing neurons that project to a caudal particular region of the lateral septum (LS). Furthermore, activation of PeFAH by using pharmacogenetic procedure induced defensive burying and enhanced approach toward a novel object, indicating a possible involvement of PeFAH for the will regulation. In the present study, we will manipulate the activity of Ucn3/Enk neurons specifically in the PeFAH to clarify the neural mechanism of will enhancement.

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  Yoko YAZAKI-SUGIYAMA

  Neuronal Mechanism of Critical Period Unit, Okinawa Institute of Science and Technology (OIST) Graduate University
  

  Research projects

  Motivational control of memory formation in zebra finch song learning.

  Research projects
  Motivational control of memory formation in zebra finch song learning.
  
  Research abstract
  Sensory information processing can be modulated depending on behavioral states of animals, such as motivation or attention, that regulate higher cognitive function, such as learning. As in human speech acquisition, songbirds learn to sing from early auditory experiences with adult tutors. Zebra finches, which have served as a premier songbird model, actively learn through social communication with their tutors, but when listening passively, they do not readily acquire the capacity to sing appropriately. Those raise the possibility that zebra finches’ behavioral state modulates auditory information processing, which regulates song learning. In this study, we will investigate neuronal mechanisms underlying how motivation regulate which memories to be formed during song learning. Recently we found the neuronal substrate of tutor song memory in the higher-level auditory cortex of juvenile zebra finches, which exhibits highly selective auditory responses to the tutor song. We will examine whether experience-dependent auditory activity in the higher-level auditory cortex is modulated by behavioral states. We will further focus on neuromodulators involved in motivation or attention to reveal the neuronal mechanism underlying the motivational control of zebra finch song learning.

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  Atsushi SEKIGUCHI

  Department of Psychosomatic Research, National Institute of Mental Health, National Center of Neurology and Psychiatry

  Research projects

  Impairement of "power of will" clarified by brain imaging data, and an attempt to enhance by an interoceptive training

  Research projects
  Impairement of "power of will" clarified by brain imaging data, and an attempt to enhance by an interoceptive training
  
  Research abstract
  In a recent stressful society, it is assumed that "power of will" is impaired. The impairment of "power of will" would cause not only mental illness, but also inappropriate managements of lifestyle. We are afraid that it would increase the risk of future cerebrovascular disorder and dementia.
  In this research, we assume that "power of will" is decreasing due to psychosocial stress. We will assess two types of index "Irrationality" and "Loss aversion" as evaluations of "the power of will" over participants of a cohort study conducted by Tohoku Medical Megabank Organization, and traumatized subjects including PTSD patients.
  Through this research, we will show that the impairment of "the power of will" is a valuable concept as an intermediate phenotype of various diseases including mental illnesses and lifestyle-related diseases like metabolic syndrome.
  Furthermore, based on an additional hypothesis that "the power of will" is influenced by "interoceptive awareness", we plan to enhance "the power of will" by conducting a cognitive intervention using an interoceptive training.
  

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  Rui NOUCHI

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

  Research projects

  Benefits of acute nutrition, cognitive, and exercise interventions on well dynamics

  Research projects
  Benefits of acute nutrition, cognitive, and exercise interventions on well dynamics
  
  Research abstract
  Motivations and concentrations on the real parts affect the successes. For example, people in low motivations or concentrations would show lower performaces. On the other hand, people in high motivations or concentrations may show beter performance. Therefore, managing motivations and concentration is important elements of success. The purpose of this study is to investigate benefits of simple cognitive, exercise, and nutrition management methods on one’s motivations and concentrations. The final goal of this study is to demonstrate the presence of these simple motivation or concentration management methods on daily behaviors (e.g. car driving) and actual tests performances (e.g. regular exam at school or sport).

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  Ken’ichiro NAKASHIMA

  Department of Psychology, Graduate School of Education, Hiroshima University
  

  Research projects

  How to develope“don’t give up”: Proposal of an intervention program for willpower

  Research projects
  How to develope“don’t give up”: Proposal of an intervention program for willpower
  
  Research abstract
  The mind of “don’t give up”is needed to find a positive way in adversity. In previous research, low socioeconomic status impairs this mind, and therefore leads to some problems about physical and mental health. Researcher has to propose the way to resolve these problems.
  In this point, an principal investigator showed that “Shift-Persist approach”was effective to maintain“don’t give up”for people in low socioeconomic status. Shifting is hypothesized to involve cognitive reappraisals as a form of emotion regulation, and persisting is hypothesized to develop purpose in life and maintain the hope that, despite adversity, the future may be better. Importantly, this combination of shifting and persisting is adaptive specifically for dealing with adversity.
  Based on these suggestions, the present study proposes an intervention program for shifting and persisting, and investigates its effectiveness.
  

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  Kazuki HYODO

  Physical Fitness Research Institute, Meiji Yasuda Life Foundation of Health and Welfare

  Research projects

  Development of mood-enhancing mild exercise program for improving executive function in older adults

  Research projects
  Development of mood-enhancing mild exercise program for improving executive function in older adults
  
  Research abstract
  The prefrontal cortex shows structural and functional decline in aging, which would be associated with decrease in motivation and executive function. Previous studies have shown that moderate- or high- intensity aerobic exercise has beneficial effect on prefrontal cortex function in older adults. However, these exercise conditions are not appropriate for the majority of elderly people due to several physical and psychological barriers.
  Recently, we observed that low intensity exercise improved executive task performance via task-related increases in prefrontal activation, and that this effect was modulated by changes in the positive mood. From these findings, it is possible that exercise which enhance positive mood could improve executive function effectively.
  In this study, we aim to clarify an effective low intensity exercise program for executive function in older adults. In order to attain the goal of this study, we will develop mood-enhancing low intensity exercise program by focusing on light rhythmic exercises, which are familiar and easy to perform for older adults. Then we will examine the acute and chronic effect of the exercise on executive function and the underlying neural mechanism by using functional near infrared spectroscopy.