金沢大学
≫Clinical Research on Social Recognition and Memory
 Prof. Mitsuru Kikuchi
 Assoc. Prof. Hirokazu Kumazaki
Research Center for Child Mental Development Kanazawa University is closely cooperated with Department of Child and Adolescent Psychiatry, Kanazawa University Hospital. The most basic policy is thinking from the view point of patients and their parents. We are always snuggled up to our patients, think with our patients, come to grip with our patients. Our Department seeks to engage in a broad spectrum of child and adolescent psychiatric intervention, research and clinical services. Our two flag is early identification for children with ASD using MEG which is specialized for infant and intervention for children with ASD using humanoid.
We always keep in mind two missions, a continuous search for new acquirement, sensitivity to the needs of patients, students and the community. We keep our promise to emphasize the importance of clinical research and facilitate the rapid integration of findings into the care of patients. We also expand the scientific foundations of autism to encompass prevention, service, policy and outcome research. We will make a contribution to the advancement of the science for autism.
≫Basic Research on Social Recognition and Memory
 Prof. Haruhiro Higashida
 Assoc. Prof. Chiharu Tsuji
Autism spectrum disorders (ASDs) are neuropsychiatric conditions characterized by impairments in social interactions, social communication, and the presence of repetitive behaviors and restricted interests, with or without associated intellectual disability. On social impairments of patients with ASDs, a huge amount of research has focused on oxytocin (OT), a cyclic nonapeptide hormone. OT is secreted into the brain from oxytocin-synthetizing (oxytocinergic) neurons in the hypothalamus and functions as a neurotransmitter and/or neuromodulator. OT plays important roles in social recognition, social memory, and social behaviors with mutual interaction. Our concern is how OT is released into the brain from the cell soma, axons, and dendrites of neurosecretory cells in the hypothalamus. We showed that locally released OT can activate OT receptors, form inositol-1,4,5-trisphosphate and elevate intracellular free calcium (Ca2+) concentrations ([Ca2+]i) in self and neighboring neurons in the hypothalamus, resulting in further OT release: i.e., autocrine or paracrine systems of OT-induced OT release. CD38-dependent cyclic ADP-ribose (cADPR) is also involved in this autoregulation by elevating [Ca2+]i via Ca2+ mobilization through ryanodine receptors on intracellular Ca2+ pools that are sensitive to both Ca2+ and cADPR. In addition, we reported that heat stimulation and hyperthermia enhance [Ca2+]i increases by Ca2+ influx probably through TRPM2 cation channels, suggesting that cADPR and TRPM2 molecules act as Ca2+ signal amplifiers. Thus, OT release is not simply due to depolarization–secretion coupling. Both of these molecules play critical roles not only during labor and milk ejection in reproductive females, but also during social behavior in daily life in both genders. This was clearly demonstrated in CD38 knockout mice in that social behavior was impaired by reduction of [Ca2+]i elevation and subsequent OT secretion. Now we extend our interests to collect evidence for the associations of CD38 with social behavior and psychiatric disorder especially in subjects with ASD.
≫Communicative Support Development
 Prof. Manabu Oi
 Assoc. Prof. Yukiko Araki
 Assis. Prof. Takashi Ikeda
Individuals with autism spectrum disorder tend to fail in comprehension of self and other, and to show difficulty in affective contact and lack of imagination. These lead to fatal blow to social adaptation in those individuals.
In the division of communicative support development, research has been conducted in regard to tasks seen below.
 Assessment and intervention of communication using Conversational Analysis.
 Developing Japanese version of Children’s Communication Checklist-2.
 Developing computer tasks which measure reception of prosody of language.
 Influence of multilingual environment on communication development in children with autism spectrum disorder.
≫Genetics and Genomics
 Prof. Shigeru Yokoyama
 Prof. Osamu Hori
Our mission is to apply genetic insights to both the basic understanding of neurodevelopment and clinical practice of psychiatry. We are currently focusing on the following projects:
#1: Genetic profiling to develop biomarkers for neurodevelopmental disorders. We are collecting genetic information, including single-nucleotide polymorphisms (SNPs) copy number variations (CNVs), in patients with autism spectrum disorders (ASDs) and healthy volunteers.
#2: To clarify the influence of genetic variation on susceptibility and progression of neurodevelopmental disorders. We are currently reconstituting variant neurotransmitter and hormone receptors, such as oxytocin and vasopressin receptors, in cultured cell lines and investigating how downstream signaling pathways are altered.
#3: To understand the role of inflammation in neurodevelopmental disorders. Using rat models of ASDs, we are exploring the potential in vivo role of cytokines and hormones in both typical and abnormal brain development.
≫Age 2 Project
 Center Director, Prof. Yoshio Minabe
The foundation of mind in a child starts with sensory and motor interaction with the world. The brain is built from the bottom up and this starts with movement and sensory exploration. In addition, human mind is built through inter-human interaction (e.g., mother and infant). The maturation of top-down pathway also plays an important role for the development of complex and efficient human mind. This is at the core of everything we do at “Division of Age 2 Project”.
Now, using child custom-sized magnetoencephalography, we research into the auditory sensory processing system and its impact on the development of sociality and language performance in young children (from 3 month young children).
≫Brain and Cognitive Individuality
 Prof. Mitsuru Kikuchi
 Assoc. Prof. Daisuke Saito
 Assis. Prof. Yuko Yoshimura
The hallmark of an enlightened society is its inclusion of more diversified behaviours and phenotypes, such as disabilities. For instance, enlightened governments have spent time and money to accommodate people with visual and hearing impairments, helping them to navigate public places and find employment. Our division makes it a goal to facilitate the same steps for autistics through scientific approach. We try to do more than simply study autistic deficits. By emphasizing the abilities and strengths of people with autism, deciphering how autistics learn and succeed in natural settings, we try to help shape the entire discussion.
≫ Translational Neuroscience Laboratory for Neurodevelopmental Disorders
 Assoc. Prof. Takanori Hashimoto
Schizophrenia is a severe mental disorder that affects about 1% of the world’s population. The pathogenesis of this illness is thought to start during early brain development and affected individuals often come to clinical attention during late adolescence and early adulthood. Psychotic symptoms, such as delusion, hallucination, and disorganized behavior, are a striking feature of this disorder. However, even more serious problem for patients is chronic impairments in social and occupational functioning, and these impairments are associated with cognitive deficits. Patients typically exhibit deficits in diverse cognitive functions, such as sensory processing, working memory, and executive function. They are resistant to currently available treatments and they are a key determinant of patients’ functional outcome.

Human cognitive functions are mediated by neural networks that consist of multiple brain regions, including different areas of the cerebral cortex. These areas are connected by axons of projecting neurons, and information processing within each and across these areas is facilitated by neural oscillations, which reflect coordinated activities of local neuron assemblies. Neural oscillations were shown to promote local information processing and global information processing through their inter-areal synchronization. Neural oscillations depend on one of the three subsets of cortical GABA neurons, that is the parvalbumin-expressing subset. PV neurons give divergent inhibitory innervations to neighboring pyramidal neurons and can synchronize firing of these neurons (Figure).

KCNS3 encodes a voltage-gated potassium channel subunit and is selectively expressed in PV neurons in the human cerebral cortex. KCNS3 subunit-containing potassium channels make EPSP fast in PV neurons and appear to contribute to neural oscillations (Figure). We have recently found that KCNS3 and KCNB1 expression levels were lower in prefrontal PV neurons in schizophrenia. Reduced KCNS3 subunit-containing channels could make EPSP slow in PV neurons and contribute to abnormal neural oscillations and cognitive deficits in schizophrenia.

In order to prove our hypothesis of KCNS3 in the pathophysiology of schizophrenia and to identify molecular targets of new therapeutic intervention for cognitive impairments, we are currently generating genetically engineered mice with PV neuron selective knockout of Kcns3. We will analyze neural oscillations and cognitive functions in these mice.
≫Psychological studies on Brain Individuality
 Prof. Haruyuki Kojima
This division aims to seek psychological mechanisms how people behave in our daily lives. Although we all have more or less “similar” brain and physical tissues/systems, we show individual differences each other when we see, draw attention, learn, feel, understand, think and behave. We measure people’s cognitive/behavioral performance with techniques of Experimental Psychology as well as monitor brain activation with brain imaging techniques (EEG/ERP, NIRS, fMRI). Then, we try to model the system of brain mechanism to explain the general properties, the regularities and the differences of human cognition/behavior.
≫Bank of Genetic Resources
 Prof. Shigeru Yokoyama
We have been depositing genetic samples from patients with autism spectrum disorders and healthy volunteers for use in integrative research. The samples include DNA obtained from blood, nails, buccal cells or saliva, and RNA and plasma from blood.
≫Studies on Social Behavior in Rodents
 Prof. Haruhiro Higashida
Oxytocin (OT) is axo-dendritically secreted into the brain from OT-containing neurons, which causes excitation by activating the OT receptors on neurons in the hypothalamus and other social brain regions. The positive feedback system of OT-induced OT release in the brain is crucial for social recognition and behavior in the daily lives of both genders. We previously showed that disruption of the OT system causes impaired social recognition and mutual interactions in mice, which can be a model rodent with psychiatric disorders, such as autism spectrum disorders (ASDs). We study the molecular mechanisms for how brain OT is released, by using CD38 or CD157 knockout mice with social amnesia, anxiety, and impaired maternal behaviors. Recently, we focus on the molecular mechanisms how brain OT is released during social stress and hyperthermia and by NAD, because it has been reported that NAD precursors are elements to activate cell (mitochondrial) activity, and that a single dose of suramin, a century-old drug for African sleeping sickness, has eliminated autism symptoms in adult mice, and that scientists found that 83% of children with ASD showed temporary improvement during a high fever.
≫Developmental Brain Functional Imaging
 Prof. Mitsuru Kikuchi
 Assis. Prof. Yuko Yoshimura
This division aims to seek psychological mechanisms how people behave in our daily lives. Although we all have more or less “similar” brain and physical tissues/systems, we show individual differences each other when we see, draw attention, learn, feel, understand, think and behave. We measure people’s cognitive/behavioral performance with techniques of Experimental Psychology as well as monitor brain activation with brain imaging techniques (EEG/ERP, NIRS, fMRI). Then, we try to model the system of brain mechanism to explain the general properties, the regularities and the differences of human cognition/behavior.
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