筑波大学大学院 人間総合科学学術院 人間総合科学研究群
Degree Programs in Comprehensive Human Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba ニューロサイエンス学位プログラム 博士前期課程・後期課程
Master's and Doctoral Programs in Neuroscience

統合失調症や自閉症などの精神神経疾患には病態の理解に基づく根本的治療法がなく、多くの患者さんが症状と社会不適応に悩んでいます。これらの疾患の背景にはニューロンの機能や形態の異常が存在し、それは遺伝要因と環境要因の複合的な影響によってもたらされます。私たちは精神神経疾患の病態を分子レベルで解明し、治療や予防へと繋げることを目標に、以下のテーマに注目して研究を行っています。

1. ニューロンの細胞内輸送機構
2. ニューロンの細胞内輸送の破綻と精神神経疾患
3. 免疫異常と脳の発達・機能異常
4. 精神神経疾患のマウスモデル研究

Our goal is to elucidate the pathogenesis and pathophysiology of schizophrenia and autism. In these illnesses, neuronal morphology and function are affected by a combination of genetic and environmental factors. A better understanding of the molecular mechanisms underlying these illnesses is important as it will lead to the future development of novel methods of treatment and prevention. Our current research is focusing on the following four areas:

1. Mechanisms of intracellular transport in neurons.
2. Mental illnesses based on the disruption of intracellular transport machinery.
3. Neuronal abnormalities caused by immunological abnormalities.
4. Analysis of mouse model of mental illnesses.

ヒトひとりひとりの遺伝子は基本的に不変です．言い換えるならば，ヒトの遺伝子配列そのものは，生涯ほとんど変化しません．ところが，脳疾患，中でも精神疾患・神経変性疾患では，あたかも遺伝子が変化・破綻したかのような症状が現れることが知られています．遺伝子配列は変化しないのに，どうしてそのようなことが起きるのでしょうか？近年，分子生物学が急速に進展した結果，その謎を解く鍵が「DNAのメチル化」にあることが判ってきました．私たちは，脳（主に神経細胞）のゲノムにおけるDNAメチル化を調べることで，アルツハイマー病に代表される神経変性疾患の分子レベルでの包括的な理解を目指しています．ゲノム脳科学に興味のある方の参加を待っています．

The mechanisms and pathogenesis of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, and psychiatric disorders, such as schizophrenia and depression, are still largely unknown, and effective treatments have not been developed. Recent studies using the patient's brains have shown that DNA methylation in the brain caused by external stimuli may be closely related to the onset and pathology of these diseases. We will examine which methylated gene regions may be involved in the pathogenesis, and aim for the development of effective treatments for these diseases.

我々の研究室では、注意や記憶、推論、学習、意思決定などの心理現象を実現する脳のメカニズムを解明することを目的としています。そのため、ヒトに近い脳の構造を持つサルに様々な認知行動課題をおこなわせ、その際に脳がどうのように活動するのかを電気生理学的な手法を用いて調べています。また、その活動を薬理学的、光・化学遺伝学的に操作することにより、脳の活動が行動制御に果たす役割を解析しています。特に現在は、その機能異常が精神疾患とも深く関わるモノアミン神経群に着目し、これらの神経群が心理現象に果たす役割を神経回路レベルで研究しています。

The goal of our research is to understand neural mechanisms underlying cognition such as attention, memory, prediction, learning and decision making. In particular, we are investigating the role of monoamine systems, such as dopamine and serotonin, in cognitive functions. Experiments in our laboratory center on the brain of awake behaving monkeys as a model for similar systems in the human brain. Using electrophysiological, pharmacological, optogenetic and chemogenetic techniques, we examine what signals monoamine neurons convey while monkeys are performing cognitive tasks and how the signals, released monoamine, work in targeted brain areas to achieve the tasks. These studies will provide more mechanistic accounts of cognitive disorders.

We are interested in neuropeptides, which play a variety of roles in regulation of the central nervous system. We have tried to identify novel neuropeptides by various biochemical searches, and define their physiological functions by neuroscientific approaches. Through these processes, we are currently performing researches in:

1. Deciphering the neuronal mechanisms that regulate sleep/wakefulness states.
2. Revealing neuronal pathways that regulate social behavior and social distance.
3. Analyzing the neuronal mechanisms that control regulated hypometabolism.

Cardiovascular and respiratory regulation by the central nervous system plays crucial roles in human homeostasis. Disorder of this regulatory system causes serious problems in a living body. Despite this, it has been remained that lots of unknown mechanisms in the cardiovascular and respiratory centers. In order to investigate these mechanisms, we are electrophysiologically approaching to mechanisms of cardiovascular and respiratory regulation by the central nervous system using in vivo preparation and in situ preparation (arterially perfused preparation) of rodents. At present, we are especially studying that I) the chemosensitive mechanism in the cardiovascular center, II) the relationship between cardiovascular and the respiratory centers (cardiorespiratory coupling), and III) diseases which induced by disorder of these systems.

Mechanisms of memory consolidation during sleep

Previous studies suggest that sleep is important for memory formation. For example, neurons that are activated during learning are re-activated during sleep. This reactivation is thought to be responsible for memory consolidation. However, its mechanism is still unclear. In rodents, each sleep episode is very short in duration, making sleep stage-specific investigation of the function of neurons technically challenging. Our group aims to overcome these challenges by utilizing the advanced techniques of optogenetics to manipulate neurons during specific stage of sleep. Our goal is to clarify the mechanisms by which neurons incorporate into memory circuits during sleep, which could contribute to the prevention or treatment of memory disorders.

当研究室では、脳が睡眠や覚醒意識を調節するための細胞・神経基盤の理解に取り組んでいます。動物の行動や脳波における特定の神経集団の機能を調べるため、神経活動操作（光遺伝学・化学遺伝学・光薬理学）、神経活動記録、in vivoイメージング（光ファイバ内視鏡）などを活用しています。現在までに、なぜコーヒーで目が覚めるのか、なぜ退屈な時に眠くなるのか、どのようにレム睡眠不足がジャンクフードへの欲求を増加させるかなどについて、成果を出してきました。また、睡眠量が極端に少ないショートスリーパーのようなマウスを作成・利用し、睡眠の機能や制御機構を調べる研究も行っています。

The investigative focus of our laboratory is the cellular and synaptic basis by which the brain regulates sleep and wakeful consciousness. Our experiments seek to link the activity of defined sets of neurons with neurobehavioral and electroencephalographic outcomes in behaving animals by using innovative genetically or chemically engineered systems (optogenetics, chemogenetics or optopharmacology) in conjunction with recording of the electrical activity produced by the brain or in-vivo imaging (e.g. fiber-optic endomicroscopy). Thereby, we made key contributions to our understanding of sleep/wake behaviors, for example, why coffee wakes us up, why we fall asleep when bored, or how REM sleep loss increases the desire for junk food.

We are interested in homeostatic sleep/wake regulation in behavioral vigilance states (e.g., mice sleep longer after when they stayed awake longer) and in cortical neural activity (e.g., a cortical region sleeps deeper when the region has been active during prior waking). Several wake, non-REM sleep, and REM sleep-promoting or -inhibiting areas have been identified. To understand the nature of the homeostatic regulation, using mice, we investigate what kind of changes the critical sleep/wake regulating centers undergo during persistent waking and subsequent sleep. As for the cortical activity, we focus on slow wave, a hallmark of NREM sleep EEG. Though it is the best marker for sleep need so far and it plays important roles in sleep-dependent memory consolidation, the underlying neural circuits remain largely unknown. Currently we investigate the role of thalamic matrix cells in slow wave generation.

Our laboratory aims to understand how sleep and sleepiness relate to the human mind and behavior. Currently, we are conducting research on two main topics. (1) Understanding sleepiness: It is well known that sleep loss causes fluctuations in response times. This phenomenon is called “state instability.” We are conducting studies to elucidate the characteristics of state instability and the neural and physiological basis of this phenomenon. In addition, we are also investigating the factors that determine “sleepiness” that cannot be explained by conventional sleep-wake models. (2) Understanding the psychological functions of sleep: This research is being conducted in order to understand the psychological functions of human sleep. In particular, we are investigating the psychological effects of sleep intervention by administering stimuli during sleep.

Behavioral Neuroscience Field is trying to clarify the biological and neural mechanisms of various human and animal behaviors. We especially focus on the neural mechanisms of learning and memory in rats: to develop methods to measure animal learning and memory, to examine the effects of brain lesions, neurotoxin treatment and drug treatment on learning and memory, to develop animal models of neural degeneration disease that includes memory disorder, and to analyze the involvement of neurotransmitter and receptor systems in memory and learning processes. We also work with the evaluation of psychotropic drugs using animal models of psychological and psychiatric diseases.

• ＊＊綾部 早穂（人間系 教授）　sahoayahuman.tsukuba.

• ＊＊Saho Ayabe (Professor, Faculty of Human Sciences)

知覚は個人の経験（記憶）に基づきます。そして、ある対象に対して、好き嫌い、快不快を感じることは、多くの場合は、この対象をどのように知覚するのかということに依存します。また知覚は文脈の影響も強く受けます。知覚学習、記憶、快不快感、構え、文脈、感覚間相互作用をキーワードに、様々な感覚モダリティ（特に、嗅覚と味覚）を通して、ヒトの知覚の機序の解明に近づくことを研究の目標としています。

Perception is based on individual experience (memory). The likeness or pleasantness of an object in the external environment often depends on how the object is perceived. Perception is also strongly influenced by context. The research goal of our lab. is to approach the elucidation of the mechanism of human perception through various sensory modalities (especially, olfaction and taste sensation), using perceptual learning, memory, hedonics, set, context, and inter-sensory interaction as keywords.

Many thinker have considered animal mind or soul for a long time. Animal psychology as an academic discipline arised from the situation in which Darwinism prevailed and systematic experimental research started at the end of 19th century. Studies in animal psychology approach the problem of animal mind through examining (1) proximal causes, (2) development, (3) functions, and (4) evolution of observable behaviors of animals. We investigate the nature of mouse mind mainly from (1) and (2), in some extent from (3) as well. The following themes are in progress.

1. Effects of rearing conditions on social behaviors of male mice.
2. Relationship between spatial structure of novel situations and habituation in locomotor activities.
3. Properties of visual perception in mice.

現代社会ではうつ病や発達障害、認知症といった、いまだ病気の全体像が解明されていない疾患に悩まされる患者様が数多くいらっしゃいます。この「脳」と「こころ」の相互作用により引き起こされる症状を明らかにするためには薬理学、生理学、分子遺伝学、神経画像学などに基づく生物学的側面と、精神病理学、心理学などに基づく心理学的側面の両方に対する深い知識と理解が必要です。我々の研究グループでは精神疾患の病因を明らかにし、よりよい治療法を開発するために日夜研究を行っております。都心から45分という利便性があり、科学と自然と文化のバランスのとれたこのつくばの地で、新たな精神医療の発展につながるような研究に共に取り組んでいきましょう。

Nowadays, there are many patients suffering from the diseases of which the whole aspect has not yet been elucidated, such as depression, neurodevelopmental disorders, and dementia. To clarify the symptoms caused by the interaction between the "brain" and "feeling", pharmacology, physiology, molecular genetics, neuroimaging and other biological aspects, as well as psychopathology and psychology were fully required. Our research group work to elucidate the etiology of mental illness and to develop better treatments. Let's work together on research that will lead to the development of new psychiatric care in this Tsukuba area that is 45 minutes from the city center and has a balance between science, nature and culture.

Our laboratory has been mainly studying psychosocial approaches for people with dementia, and the development of assessments to examine their effects, for a long time. It is important for us to bridge evidence with practices. We welcome students and researchers interested in the following academic themes which are being studied in my laboratory:

1. Psychosocial approaches for people with dementia
2. Structured group activities for people with dementia, such as cognitive stimulation and reminiscence therapy
3. Individual interventions to challenging behaviors in people with dementia, such as applied behavioral analysis and cognitive behavioral therapy
4. Assessments to understand everyday conditions of cognitions, mood, and behaviors of people with dementia, with which we study the effects of interventions
5. People’s image of aging and dementia, and the enlightenment based on such results

People with deficits in processing of spoken and/or written language have various difficulties in school, work, and daily life. To provide effective supports and treatments, deep understanding of symptoms and causes is important. We aim to clarify underlying mechanisms of deficits in language processing and develop scientific evidence-based supports and treatments, using cognitive neuropsychological methods. Our current research is focusing on the following:

1. Research on underlying mechanisms of deficits in language processing
2. Development of tests to detect symptoms and cognitive deficits
3. Development of effective supports and treatments based on symptoms and cognitive characteristics

• #岡崎 慎治（人間系 准教授）

• #Shinji Okazaki (Associate Professor, Faculty of Human Sciences)

Our goal is to understand the molecular and cellular mechanisms that underlie synaptic connectivity, neural circuit formation, and brain homeostasis during the postnatal stage. Particularly, we are interested in understanding the functional relationship between neurons and microglia. The ongoing projects are as follows;

1. Neuron-microglia communication during the developmental stage.
2. Synaptic connectivity and brain homeostasis regulated by genes associated with ASD.
3. Regulation of body temperature mediated by environmental change after birth.
4. Drug discovery for regulating microglial activity.

• 秋山 英三（システム情報系 教授）

• Eizo Akiyama (Professor, Faculty of Engineering, Information and Systems)

Our research goal is to understand the physiological and anatomical mechanisms underlying higher brain functions. We are working on several research topics regarding functional organization and plasticity of brain networks. From a neurorehabilitation perspective, some studies are focusing on the recovery of impaired brain function.

1. Neuromodulation & Neurorehabilitation
2. Functional neuroimaging & Functional architecture of the brain
3. Multisensory integration and segregation in the brain
4. Temporal dynamics of face recognition in the inferior temporal cortex
5. Artificial intelligence and Brain-machine interface

製品や環境に対するユーザビリティを検討する上で、脳科学的な観点からユーザの知覚・認知特性を理解することは非常に重要です。当研究グループでは、よりよい製品やサービスのデザインを目指して、脳活動や行動指標による人間の知覚・認知特性の解明や評価技術の開発を行っています。脳活動計測の手段として、認知課題遂行中の事象関連脳電位（ERP）や機能的磁気共鳴画像（fMRI）などを用います。また、実験室内での研究にとどまらず、実環境でのユーザ評価（自動車運転中のドライバ評価など）の研究も行っています。当研究グループは国立研究開発法人産業技術総合研究所との連携大学院方式で設置されており、研究活動は産業技術総合研究所において行います。

Our research group focuses on the understanding of human perception and cognition by measuring brain activities (e.g., event-related potentials and functional MRI) and behavior to develop techniques to design better products and services. We perform experiments not only under the laboratory settings but also under the real-world environments such as vehicle driving. Our research group is located at National Institute of Advanced Industrial Science and Technology (AIST); students take the classes at University of Tsukuba and carry out their researches at AIST (Cooperative Graduate School Program).

There are large individual differences in many behavioral phenotypes, such as emotionality, aggression, sociability and stress-susceptibility in the mouse (Mus musculus). My research interest is to understand biological mechanisms that produce these individual differences in social behavior, especially aggressive behavior, from multi-dimensional aspects including gene, neural circuit, immune system, and microbiota.

The brain reconstructs the external world by collecting multiple sensory signals. To understand the neural information processing in perception and cognition, we focus on how multisensory signals are integrated and segregated in the brain and how they represent spatial and temporal information. To answer these questions, we perform psychophysical, physiological, and pharmacological experiments in human and animals. We are also examining the effects of local brain temperature on perception and cognition.

Experimental psychology and neuroscience, traditionally have investigated sensory modalities in isolation (vision on its own, audition on its own, touch in its own, etc.). However, in the “real world” all our senses work at-the-same-time (or multisensory). All this information is processed in parallel by the bran to build a representation of the external world. Our goal is investigating how this process occurs.