Researchers Database

Yokoyama Chihiro

FacultyFaculty Division of Human Life and Environmental Sciences Research Group of Environmental Health
Last Updated :2022/06/30


Profile and Settings

  • Name (Japanese)

  • Name (Kana)


Research Interests

  • 学習セット
  • ストレス
  • 遺伝子多型
  • 神経科学
  • 逆転学習
  • 発達
  • 扁桃体
  • 図形弁別課題
  • 下部側頭葉
  • 攻撃性
  • ドーパミン
  • コモンマーモセット
  • 個体間コミュニケーション
  • 社会性
  • 養育環境
  • 前頭前皮質
  • 問題解決
  • 免疫組織化学
  • PET
  • セロトニン

Research Areas

  • Life sciences, Pathobiochemistry
  • Life sciences, Neuroscience - general
  • Life sciences, Neuroanatomy and physiology
  • Life sciences, Psychiatry

Research Experience

  • Apr. 2021, 9999, Nara Women’s University, Faculty Division of Human Life and Environmental Sciences, 教授
  • Jul. 2015, Mar. 2021, 国立研究開発法人理化学研究所, 脳コネクトミクス研究チーム, 上級研究員
  • Apr. 2013, Jun. 2015, RIKEN, 分子プローブ機能評価研究チーム, 副チームリーダー
  • Apr. 2006, Mar. 2013, RIKEN, 分子プローブ機能評価研究チーム, 研究員
  • Apr. 2002, Mar. 2006, Kyoto Prefectural University of Medicine, 精神機能病態学, 講師
  • Oct. 1998, Mar. 2002, 財団法人 大阪バイオサイエンス研究所, 第3研究部, 研究員
  • Apr. 1996, Sep. 1998, Kawasaki Medical School, 解剖学教室, 講師
  • Apr. 1994, Mar. 1996, Kyoto Prefectural University of Medicine, 第二解剖学教室, 助手
  • May 1988, Mar. 1990, 京都府立医科大学付属病院 研修医 精神医学教室


Published Papers

  • Refereed, NeuroImage, Anatomical variability, multi-modal coordinate systems, and precision targeting in the marmoset brain., Takayuki Ose; Joonas A Autio; Masahiro Ohno; Stephen Frey; Akiko Uematsu; Akihiro Kawasaki; Chiho Takeda; Yuki Hori; Kantaro Nishigori; Tomokazu Nakako; Chihiro Yokoyama; Hidetaka Nagata; Tetsuo Yamamori; David C Van Essen; Matthew F Glasser; Hiroshi Watabe; Takuya Hayashi, Localising accurate brain regions needs careful evaluation in each experimental species due to their individual variability. However, the function and connectivity of brain areas is commonly studied using a single-subject cranial landmark-based stereotactic atlas in animal neuroscience. Here, we address this issue in a small primate, the common marmoset, which is increasingly widely used in systems neuroscience. We developed a non-invasive multi-modal neuroimaging-based targeting pipeline, which accounts for intersubject anatomical variability in cranial and cortical landmarks in marmosets. This methodology allowed creation of multi-modal templates (MarmosetRIKEN20) including head CT and brain MR images, embedded in coordinate systems of anterior and posterior commissures (AC-PC) and CIFTI grayordinates. We found that the horizontal plane of the stereotactic coordinate was significantly rotated in pitch relative to the AC-PC coordinate system (10 degrees, frontal downwards), and had a significant bias and uncertainty due to positioning procedures. We also found that many common cranial and brain landmarks (e.g., bregma, intraparietal sulcus) vary in location across subjects and are substantial relative to average marmoset cortical area dimensions. Combining the neuroimaging-based targeting pipeline with robot-guided surgery enabled proof-of-concept targeting of deep brain structures with an accuracy of 0.2 mm. Altogether, our findings demonstrate substantial intersubject variability in marmoset brain and cranial landmarks, implying that subject-specific neuroimaging-based localization is needed for precision targeting in marmosets. The population-based templates and atlases in grayordinates, created for the first time in marmoset monkeys, should help bridging between macroscale and microscale analyses., 15 Apr. 2022, 250, 118965, 118965, Scientific journal, True
  • Refereed, NeuroImage, Comparative connectomics of the primate social brain., Chihiro Yokoyama; Joonas A Autio; Takuro Ikeda; Jérôme Sallet; Rogier B Mars; David C Van Essen; Matthew F Glasser; Norihiro Sadato; Takuya Hayashi, Social interaction is thought to provide a selection pressure for human intelligence, yet little is known about its neurobiological basis and evolution throughout the primate lineage. Recent advances in neuroimaging have enabled whole brain investigation of brain structure, function, and connectivity in humans and non-human primates (NHPs), leading to a nascent field of comparative connectomics. However, linking social behavior to brain organization across the primates remains challenging. Here, we review the current understanding of the macroscale neural mechanisms of social behaviors from the viewpoint of system neuroscience. We first demonstrate an association between the number of cortical neurons and the size of social groups across primates, suggesting a link between neural information-processing capacity and social capabilities. Moreover, by capitalizing on recent advances in species-harmonized functional MRI, we demonstrate that portions of the mirror neuron system and default-mode networks, which are thought to be important for representation of the other's actions and sense of self, respectively, exhibit similarities in functional organization in macaque monkeys and humans, suggesting possible homologies. With respect to these two networks, we describe recent developments in the neurobiology of social perception, joint attention, personality and social complexity. Together, the Human Connectome Project (HCP)-style comparative neuroimaging, hyperscanning, behavioral, and other multi-modal investigations are expected to yield important insights into the evolutionary foundations of human social behavior., 31 Oct. 2021, 245, 118693, 118693, Scientific journal, True
  • Refereed, PloS one, Personality, subjective well-being, and the serotonin 1a receptor gene in common marmosets (Callithrix jacchus)., Alexander Weiss; Chihiro Yokoyama; Takuya Hayashi; Miho Inoue-Murayama, Studies of personality traits in common marmosets (Callithrix jacchus) indicate that there are five or six constructs-Sociability, Dominance, Neuroticism, Openness, and two related to Conscientiousness. The present study attempted to determine whether our earlier study of laboratory-housed individuals only yielded three-Dominance, Sociability, and Neuroticism-because of a low amount of between-subjects variance. To do so, we increased our sample size from 77 to 128. In addition, we ascertained the reliability and validity of ratings and whether polymorphisms related to the serotonin 1a receptor were associated with personality. We found Sociability, Dominance, and Negative Affect factors that resembled three domains found in previous studies, including ours. We also found an Openness and Impulsiveness factor, the latter of which bore some resemblance to Conscientiousness, and two higher-order factors, Pro-sociality and Boldness. In further analyses, we could not exclude the possibility that Pro-sociality and Boldness represented a higher-level of personality organization. Correlations between personality factors and well-being were consistent with the definitions of the factors. There were no significant associations between personality and genotype. These results suggest that common marmoset personality structure varies as a function of rearing or housing variables that have not yet been investigated systematically., 2021, 16, 8, e0238663, Scientific journal, True
  • Refereed, Nature communications, Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues., Etsuo A Susaki; Chika Shimizu; Akihiro Kuno; Kazuki Tainaka; Xiang Li; Kengo Nishi; Ken Morishima; Hiroaki Ono; Koji L Ode; Yuki Saeki; Kazunari Miyamichi; Kaoru Isa; Chihiro Yokoyama; Hiroki Kitaura; Masako Ikemura; Tetsuo Ushiku; Yoshihiro Shimizu; Takashi Saito; Takaomi C Saido; Masashi Fukayama; Hirotaka Onoe; Kazushige Touhara; Tadashi Isa; Akiyoshi Kakita; Mitsuhiro Shibayama; Hiroki R Ueda, Whole-organ/body three-dimensional (3D) staining and imaging have been enduring challenges in histology. By dissecting the complex physicochemical environment of the staining system, we developed a highly optimized 3D staining imaging pipeline based on CUBIC. Based on our precise characterization of biological tissues as an electrolyte gel, we experimentally evaluated broad 3D staining conditions by using an artificial tissue-mimicking material. The combination of optimized conditions allows a bottom-up design of a superior 3D staining protocol that can uniformly label whole adult mouse brains, an adult marmoset brain hemisphere, an ~1 cm3 tissue block of a postmortem adult human cerebellum, and an entire infant marmoset body with dozens of antibodies and cell-impermeant nuclear stains. The whole-organ 3D images collected by light-sheet microscopy are used for computational analyses and whole-organ comparison analysis between species. This pipeline, named CUBIC-HistoVIsion, thus offers advanced opportunities for organ- and organism-scale histological analysis of multicellular systems., 27 Apr. 2020, 11, 1, 1982, 1982, Scientific journal, True
  • Refereed, Scientific reports, Common marmoset (Callithrix jacchus) personality, subjective well-being, hair cortisol level and AVPR1a, OPRM1, and DAT genotypes., Miho Inoue-Murayama; Chihiro Yokoyama; Yumi Yamanashi; Alexander Weiss, We studied personality, subjective well-being, and hair cortisol level, in common marmosets Callithrix jacchus, a small, cooperatively breeding New World monkey, by examining their associations with one another and genotypes. Subjects were 68 males and 9 females that lived in the RIKEN Center for Life Science Technologies. Personality and subjective well-being were assessed by keeper ratings on two questionnaires, hair samples were obtained to assay cortisol level and buccal swabs were used to assess AVPR1a, OPRM1 and DAT genotypes. Three personality domains-Dominance, Sociability, and Neuroticism-were identified. Consistent with findings in other species, Sociability and Neuroticism were related to higher and lower subjective well-being, respectively. Sociability was also associated with higher hair cortisol levels. The personality domains and hair cortisol levels were heritable and associated with genotypes: the short form of AVPR1a was associated with lower Neuroticism and the AA genotype of the A111T SNP of OPRM1 was related to lower Dominance, lower Neuroticism, and higher hair cortisol level. Some genetic associations were not in directions that one would expect given findings in other species. These findings provide insights into the proximate and ultimate bases of personality in common marmosets, other primates and humans., 06 Jul. 2018, 8, 1, 10255, 10255, Scientific journal, True
  • Refereed, Analytical biochemistry, Quantification of receptor activation by oxytocin and vasopressin in endocytosis-coupled bioluminescence reduction assay using nanoKAZ., Isao Kii; Shino Hirahara-Owada; Masataka Yamaguchi; Takashi Niwa; Yuka Koike; Rie Sonamoto; Harumi Ito; Kayo Takahashi; Chihiro Yokoyama; Takuya Hayashi; Takamitsu Hosoya; Yasuyoshi Watanabe, Oxytocin (OXT) and arginine vasopressin (AVP) are structurally similar neuropeptide hormones that function as neurotransmitters in the brain, and have opposite key roles in social behaviors. These peptides bind to their G protein-coupled receptors (OXTR and AVPRs), inducing calcium ion-dependent signaling pathways and endocytosis of these receptors. Because selective agonists and antagonists for these receptors have been developed as therapeutic and diagnostic agents for diseases such as psychiatric disorders, facile methods are in demand for the evaluation of selectivity between these receptors. In this study, we developed a quantitative assay for OXT- and AVP-induced endocytosis of their receptors. The mutated Oplophorus luciferase, nanoKAZ, was fused to OXTR and AVPRs to enable rapid quantification of agonist-induced endocytosis by bioluminescence reduction. Agonist stimulation significantly decreases bioluminescence of nanoKAZ-fused receptors in living cells. Using this system, we evaluated clinically used OXTR antagonist atosiban and a reported pyrazinyltriazole derivative, hereby designated as PF13. Atosiban acted as an antagonist of AVPR1a, as well as an agonist for AVPR1b, whereas PF13 antagonized OXTR more selectively than atosiban, as reported previously. This paper shows a strategy for quantification of agonist-induced endocytosis of OXTR and AVPRs, and confirms its potent utility in the evaluation of agonists and antagonists., 15 May 2018, 549, 174, 183, Scientific journal, True
  • Refereed, Animal cognition, Springer Verlag, Individual identity and affective valence in marmoset calls: in vivo brain imaging with vocal sound playback., Masaki Kato; Chihiro Yokoyama; Akihiro Kawasaki; Chiho Takeda; Taku Koike; Hirotaka Onoe; Atsushi Iriki, As with humans, vocal communication is an important social tool for nonhuman primates. Common marmosets (Callithrix jacchus) often produce whistle-like 'phee' calls when they are visually separated from conspecifics. The neural processes specific to phee call perception, however, are largely unknown, despite the possibility that these processes involve social information. Here, we examined behavioral and whole-brain mapping evidence regarding the detection of individual conspecific phee calls using an audio playback procedure. Phee calls evoked sound exploratory responses when the caller changed, indicating that marmosets can discriminate between caller identities. Positron emission tomography with [18F] fluorodeoxyglucose revealed that perception of phee calls from a single subject was associated with activity in the dorsolateral prefrontal, medial prefrontal, orbitofrontal cortices, and the amygdala. These findings suggest that these regions are implicated in cognitive and affective processing of salient social information. However, phee calls from multiple subjects induced brain activation in only some of these regions, such as the dorsolateral prefrontal cortex. We also found distinctive brain deactivation and functional connectivity associated with phee call perception depending on the caller change. According to changes in pupillary size, phee calls from a single subject induced a higher arousal level compared with those from multiple subjects. These results suggest that marmoset phee calls convey information about individual identity and affective valence depending on the consistency or variability of the caller. Based on the flexible perception of the call based on individual recognition, humans and marmosets may share some neural mechanisms underlying conspecific vocal perception., May 2018, 21, 3, 331, 343, Scientific journal, True
  • Refereed, The international journal of neuropsychopharmacology, OXFORD UNIV PRESS, Marmoset Serotonin 5-HT1A Receptor Mapping with a Biased Agonist PET Probe 18F-F13714: Comparison with an Antagonist Tracer 18F-MPPF in Awake and Anesthetized States., Chihiro Yokoyama; Aya Mawatari; Akihiro Kawasaki; Chiho Takeda; Kayo Onoe; Hisashi Doi; Adrian Newman-Tancredi; Luc Zimmer; Hirotaka Onoe, BACKGROUND: In vivo mapping by positron emission tomography of the serotonin 1A receptors has been hindered by the lack of suitable agonist positron emission tomography probes. 18F-labeled F13714 is a recently developed biased agonist positron emission tomography probe that preferentially targets subpopulations of serotonin 1A receptors in their "active state," but its brain labeling pattern in nonhuman primate has not been described. In addition, a potential confound in the translatability of PET data between nonhuman animal and human arise from the use of anesthetics that may modify the binding profiles of target receptors. METHODS: Positron emission tomography scans were conducted in a cohort of common marmosets (n=4) using the serotonin 1A receptor biased agonist radiotracer, 18F-F13714, compared with a well-characterized 18F-labeled antagonist radiotracer, 18F-MPPF. Experiments on each animal were performed under both consciousness and isoflurane-anesthesia conditions. RESULTS: 18F-F13714 binding distribution in marmosets by positron emission tomography differs markedly from that of the 18F-MPPF. Whereas 18F-MPPF showed highest binding in hippocampus and amygdala, 18F-F13714 showed highest labeling in other regions, including insular and cingulate cortex, thalamus, raphe, caudate nucleus, and putamen. The binding potential values of 18F-F13714 were about one-third of those observed with 18F-MPPF, with marked individual- and region-specific differences under isoflurane-anesthetized vs conscious conditions. CONCLUSIONS: These findings highlight the importance of investigating the brain imaging of serotonin 1A receptors using agonist probes such as 18F-F13714, which may preferentially target subpopulations of serotonin 1A receptors in specific brain regions of nonhuman primate as a biased agonist., Dec. 2016, 19, 12, Scientific journal, True
  • Refereed, Scientific reports, NATURE PUBLISHING GROUP, Distinct roles for primate caudate dopamine D1 and D2 receptors in visual discrimination learning revealed using shRNA knockdown., Masafumi Takaji; Atsushi Takemoto; Chihiro Yokoyama; Akiya Watakabe; Hiroaki Mizukami; Keiya Ozawa; Hirotaka Onoe; Katsuki Nakamura; Tetsuo Yamamori, The striatum plays important motor, associative and cognitive roles in brain functions. However, the rodent dorsolateral (the primate putamen) and dorsomedial (the primate caudate nucleus) striatum are not anatomically separated, making it difficult to distinguish their functions. By contrast, anatomical separation exists between the caudate nucleus and putamen in primates. Here, we successfully decreased dopamine D1 receptor (D1R) or D2R mRNA expression levels selectively in the marmoset caudate using shRNA knockdown techniques, as determined using positron emission tomography imaging with specific D1R and D2R ligands and postmortem in situ hybridization analysis. We then conducted a voxel-based correlation analysis between binding potential values of PET imaging and visual discrimination learning task performance in these genetically modified marmosets to find a critical role for the caudate D2R but no apparent role for the caudate D1R. This latter finding challenges the current understanding of the mechanisms underlying D1R activation in the caudate., 02 Nov. 2016, 6, 35809, 35809, Scientific journal, True
  • Refereed, Neuroscience research, ELSEVIER IRELAND LTD, Positron emission tomography imaging of the social brain of common marmosets., Chihiro Yokoyama; Hirotaka Onoe, Positron emission tomography (PET) is a molecular imaging modality that can visualize functional neurochemical processes throughout the brain in the living condition, and is useful in bridging the gap between experimental animals and humans. We applied PET to common marmosets to study the brain mechanisms underlying social behaviors. Common marmosets are known for their high level of sociality within a cooperative breeding system, which is rare among non-human primates, and they could represent valuable animals for studying human-like social behaviors. PET successfully revealed a brain-molecular relationship underlying social traits and a functional brain network associated with social situations in common marmosets. Marmoset PET appears likely to prove useful in understanding the neurobiological mechanisms underpinning social behaviors in both physiological and pathological conditions, and has potential for simulating psychiatric disorders., Apr. 2015, 93, 82, 90, Scientific journal, True
  • Refereed, NeuroImage, ACADEMIC PRESS INC ELSEVIER SCIENCE, A voxel-based analysis of brain activity in high-order trigeminal pathway in the rat induced by cortical spreading depression., Yilong Cui; Hiroshi Toyoda; Takeo Sako; Kayo Onoe; Emi Hayashinaka; Yasuhiro Wada; Chihiro Yokoyama; Hirotaka Onoe; Yosky Kataoka; Yasuyoshi Watanabe, Cortical spreading depression (SD) is a self-propagating wave of depolarization that is thought to be an underling mechanism of migraine aura. Growing evidence demonstrates that cortical SD triggers neurogenic meningeal inflammation and contributes to migraine headaches via subsequent activation of trigeminal afferents. Although direct and indirect evidence shows that cortical SD activates the trigeminal ganglion (peripheral pathway) and the trigeminal nucleus caudalis (TNC, the first central site of the trigeminal nociceptive pathway), it is not yet known whether cortical SD activates the high-order trigeminal nociceptive pathway in the brain. To address this, we induced unilateral cortical SD in rats, and then examined brain activity using voxel-based statistical parametric mapping analysis of FDG-PET imaging. The results show that approximately 40h after the induction of unilateral cortical SD, regional brain activity significantly increased in several regions, including ipsilateral TNC, contralateral ventral posteromedial (VPM) and posterior thalamic nuclei (Po), the trigeminal barrel-field region of the primary somatosensory cortex (S1BF), and secondary somatosensory cortex (S2). These results suggest that cortical SD is a noxious stimulus that can activate the high-order trigeminal nociceptive pathway even after cortical SD has subsided, probably due to prolonged meningeal inflammation., Mar. 2015, 108, 17, 22, Scientific journal, True
  • Refereed, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, SPRINGER, Increase in 5-HT1B receptors in nucleus accumbens and ventral pallidum by ketamine as its possible mechanism of antidepressant action: PET study with rhesus monkeys, H. Onoe; H. Yamanaka; C. Yokoyama; H. Mizuma; S. J. Finnema; H. Doi; C. Halldin, Oct. 2014, 41, S215, S215
  • Refereed, Cell, CELL PRESS, Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis., Etsuo A Susaki; Kazuki Tainaka; Dimitri Perrin; Fumiaki Kishino; Takehiro Tawara; Tomonobu M Watanabe; Chihiro Yokoyama; Hirotaka Onoe; Megumi Eguchi; Shun Yamaguchi; Takaya Abe; Hiroshi Kiyonari; Yoshihiro Shimizu; Atsushi Miyawaki; Hideo Yokota; Hiroki R Ueda, Systems-level identification and analysis of cellular circuits in the brain will require the development of whole-brain imaging with single-cell resolution. To this end, we performed comprehensive chemical screening to develop a whole-brain clearing and imaging method, termed CUBIC (clear, unobstructed brain imaging cocktails and computational analysis). CUBIC is a simple and efficient method involving the immersion of brain samples in chemical mixtures containing aminoalcohols, which enables rapid whole-brain imaging with single-photon excitation microscopy. CUBIC is applicable to multicolor imaging of fluorescent proteins or immunostained samples in adult brains and is scalable from a primate brain to subcellular structures. We also developed a whole-brain cell-nuclear counterstaining protocol and a computational image analysis pipeline that, together with CUBIC reagents, enable the visualization and quantification of neural activities induced by environmental stimulation. CUBIC enables time-course expression profiling of whole adult brains with single-cell resolution., 24 Apr. 2014, 157, 3, 726, 39, Scientific journal, True
  • Refereed, TRANSLATIONAL PSYCHIATRY, NATURE PUBLISHING GROUP, A possible mechanism of the nucleus accumbens and ventral pallidum 5-HT1B receptors underlying the antidepressant action of ketamine: a PET study with macaques, H. Yamanaka; C. Yokoyama; H. Mizuma; S. Kurai; S. J. Finnema; C. Halldin; H. Doi; H. Onoe, Ketamine is a unique anesthetic reagent known to produce various psychotic symptoms. Ketamine has recently been reported to elicit a long-lasting antidepressant effect in patients with major depression. Although recent studies provide insight into the molecular mechanisms of the effects of ketamine, the antidepressant mechanism has not been fully elucidated. To understand the involvement of the brain serotonergic system in the actions of ketamine, we performed a positron emission tomography (PET) study on non-human primates. Four rhesus monkeys underwent PET studies with two serotonin (5-HT)-related PET radioligands, [C-11]AZ10419369 and [C-11]DASB, which are highly selective for the 5-HT1B receptor and serotonin transporter (SERT), respectively. Voxel-based analysis using standardized brain images revealed that ketamine administration significantly increased 5-HT1B receptor binding in the nucleus accumbens and ventral pallidum, whereas it significantly reduced SERT binding in these brain regions. Fenfluramine, a 5-HT releaser, significantly decreased 5-HT1B receptor binding, but no additional effect was observed when it was administered with ketamine. Furthermore, pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), a potent antagonist of the glutamate alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor, blocked the action of ketamine on the 5-HT1B receptor but not SERT binding. This indicates the involvement of AMPA receptor activation in ketamine-induced alterations of 5-HT1B receptor binding. Because NBQX is known to block the antidepressant effect of ketamine in rodents, alterations in the serotonergic neurotransmission, particularly upregulation of postsynaptic 5-HT1B receptors in the nucleus accumbens and ventral pallidum may be critically involved in the antidepressant action of ketamine., Jan. 2014, 4, Scientific journal
  • Refereed, Journal of theoretical biology, ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, New index based on the physical separation of motion into three categories for characterizing the effect of cocaine in mice., Hiroto Shoji; Yasuhiro Nakatomi; Chihiro Yokoyama; Kenji Fukui; Kazumitsu Hanai, Characterization of open-field behavior and locomotor activity is widely used to assess the influence of a drug on mouse or rat behavior. In this study, we developed an index for characterizing the behavior of cocaine-administered mice (C57BL/6, DBA/2, and BALB/c). Because a three-exponential-model exhibited the best fit to the obtained data among the different probability density functions, we divided each walking episode into three categories according to the duration of movement. We found a significant difference in decay variation of mean speed with time in the case of long walking duration. To clarify this difference quantitatively, we developed an index for the changes in locomotion control, based on a heuristic argument regarding the ratio of the coefficients of the drag term obtained by the biphasic motion-equation model. The index had a significant dose-related effect in each strain and a significant strain effect in high-concentration drug. Therefore, it would thus be useful for examining the effect of the drug on locomotor activity in mice. Moreover, evaluating other characters suggested previously, the proposed index had good advantage to differentiate the dose-related response in the three species of inbred mice., 21 Sep. 2013, 333, 68, 77, Scientific journal, True
  • Refereed, Cerebral cortex (New York, N.Y. : 1991), Linkage between the midline cortical serotonergic system and social behavior traits: positron emission tomography studies of common marmosets., Chihiro Yokoyama; Akihiro Kawasaki; Takuya Hayashi; Hirotaka Onoe, Serotonin is known to play an important role not only in regulating emotional behaviors, but also in the formation of social behavior traits. To determine the location and serotonin function of brain areas involved in social behavior traits, we tested serotonin transporter (SERT) binding and neural activity linked with the social behaviors of common marmosets with positron emission tomography using [(11)C]-3-amino-4-(2-dimetylaminomethyl-phenylsulfanyl)-benzonitrile and [(18)F]fluorodeoxyglucose, respectively. Factor analysis of behavioral measures during a direct encounter between unfamiliar adult males identified three classes of social behavioral traits: (1) aggressive, (2) anxious, and (3) unfriendly (opposite of friendly). Voxel-based analysis revealed a significant association between SERT binding with the social behavioral traits in the midline cortical subregions. Aggressive and friendly traits are localized to the posterior cingulate cortex, and the anxious trait is localized to the anterior cingulate cortex. In addition, neural activity and functional connectivity of the posterior and anterior cingulate cortices appear to be altered depending on the social situation. These results suggest that the midline cortical serotonergic system is crucial in social behavior traits and its subregions are functionally segregated in socio-emotional processing., Sep. 2013, 23, 9, 2136, 45, Scientific journal, True
  • Refereed, Psychopharmacology, SPRINGER, Evaluation of dopamine D₂/D₃ and serotonin 5-HT₂A receptor occupancy for a novel antipsychotic, lurasidone, in conscious common marmosets using small-animal positron emission tomography., Shunsuke Nakazawa; Chihiro Yokoyama; Naohiro Nishimura; Tomoko Horisawa; Akihiro Kawasaki; Hiroshi Mizuma; Hisashi Doi; Hirotaka Onoe, RATIONALE: Lurasidone is a novel antipsychotic drug with potent binding affinity for dopamine D(2) and serotonin (5-hydroxytryptamine, 5-HT)(2A), 5-HT(7), and 5-HT(1A) receptors. Previous pharmacological studies have revealed that lurasidone exhibits a preferable profile (potent antipsychotic activity and lower incidence of catalepsy) to other antipsychotic drugs, although the contribution of receptor subtypes to this profile remains unclear. OBJECTIVES: To compare target engagements of lurasidone with those of an atypical antipsychotic, olanzapine, we performed evaluation of dopamine D(2)/D(3) and serotonin 5-HT(2A) receptor occupancy in vivo by positron emission tomography (PET) with conscious common marmosets. METHODS: We measured brain receptor occupancies in conscious common marmosets after oral administrations of lurasidone or olanzapine by PET with [(11)C]raclopride and [(11)C]R-(+)-α-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidine methanol (MDL 100907) for D(2)/D(3) and 5-HT(2A) receptors, respectively. RESULTS: Increases in brain D(2)/D(3) receptor occupancies of both lurasidone and olanzapine, which reached >80 % at maximum, were observed in the striatum with significant correlations to plasma drug levels. However, lurasidone showed lower 5-HT(2A) receptor occupancy in the frontal cortex within the same dose range, while olanzapine showed broadly comparable 5-HT(2A) and D(2)/D(3) receptor occupancies. CONCLUSIONS: Compared with olanzapine, lurasidone preferentially binds to D(2)/D(3) receptors rather than 5-HT(2A) receptors in common marmosets. These results suggest that the contribution of in vivo 5-HT(2A) receptor blocking activity to the pharmacological profile of lurasidone might differ from olanzapine in terms of the low risk of extrapyramidal syndrome and efficacy against negative symptoms., Jan. 2013, 225, 2, 329, 39, Scientific journal, True
  • Refereed, Neuroscience research, ELSEVIER IRELAND LTD, The food reaching test: a sensitive test of behavioral improvements by deep brain stimulation in MPTP-treated monkey., Tetsuya Asakawa; Kenji Sugiyama; Souichi Akamine; Chihiro Yokoyama; Miho Shukuri; Hiroshi Mizuma; Hideo Tsukada; Hirotaka Onoe; Hiroki Namba, We modified an objective behavioral test, namely the food reaching test (FRT), for quantitative assessment of motor performance improved by deep brain stimulation (DBS) of the subthalamic nucleus (STN) in the Parkinsonian monkeys. The symptomatic features and their severity in 3 monkeys treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were evaluated with a subjective monkey Parkinson's disease rating scale (PDRS). We then performed STN-DBS with the minimum current intensity that stopped the tremor. The time required for the monkeys to pick up all 5 pieces of potato (FRT time) was measured as a major index to evaluate bradykinesia. The success rate was adopted as another index for assessing overall motor impairments. Although both FRT time and PDRS score were similarly improved by STN-DBS, change of FRT time appeared more sensitive than that of PDRS scores. FRT is an easily trained behavioral test with high objectivity and sensitivity that can be applied for assessing motor performance in MPTP-treated monkeys during experiments in a restrained condition such as functional imaging of the brain., Oct. 2012, 74, 2, 122, 8, Scientific journal, True
  • Refereed, Journal of neural transmission (Vienna, Austria : 1996), SPRINGER WIEN, Disruption of programmed masticatory movements in unilateral MPTP-treated monkeys as a model of jaw movement abnormality in Parkinson's disease., Kazunori Adachi; Masayuki Kobayashi; Toshiyuki Kawasaki; Chihiro Yokoyama; John L Waddington; Hiroshi Sakagami; Hirotaka Onoe; Noriaki Koshikawa, While motor disturbance in Parkinson's disease can affect innate, programmed processes, such as masticatory mandibular movements, the pathophysiology of such abnormalities remains unclear. This study applies digital analysis by high-speed video signal processing that tracks three dots placed around the mouth for recording masticatory movements in unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. The system analyzes displacement, velocity and cycle duration of the topography of mandibular movement during mastication of sweet potato slices. In monkeys receiving MPTP into the right carotid artery (n = 3), positron emission tomography indicated significant reduction in the binding of (E)-N-(3-iodoprop-2-enyl)-2β-carbo[(11)C]methoxy-3β-(4-methylphenyl)nortropane ([(11)C]PE2I) to the dopamine transporter in the right caudate, putamen, nucleus accumbens and substantia nigra relative to the contralateral hemisphere. These monkeys showed hypokinesia of the left forelimbs and hindlimbs. During mastication, MPTP-treated monkeys chewed preferentially on the left side, while untreated monkeys (n = 3) showed no preference for chewing side. The amplitude of vertical opening and closing movements was reduced in MPTP-treated monkeys, with a slight but significant increase in the lateral component of mandibular movements. The velocity of all phases of horizontal mandibular movements was reduced. In consequence, duration of the occlusal phase was increased, while duration of the closing phase was decreased in MPTP-treated monkeys. These findings indicate that during masticatory movements MPTP-treated monkeys chew preferentially on the side contralateral to loss of dopamine neurons, with reduced amplitude and velocity of mandibular movements. High-speed digital movement analysis is able to define and quantify abnormalities of orofacial movement topography as a sign of parkinsonism., Aug. 2012, 119, 8, 933, 41, Scientific journal, True
  • Refereed, Journal of nuclear medicine : official publication, Society of Nuclear Medicine, SOC NUCLEAR MEDICINE INC, Developmental changes in P-glycoprotein function in the blood-brain barrier of nonhuman primates: PET study with R-11C-verapamil and 11C-oseltamivir., Tadayuki Takashima; Chihiro Yokoyama; Hiroshi Mizuma; Hajime Yamanaka; Yasuhiro Wada; Kayo Onoe; Hiroko Nagata; Shusaku Tazawa; Hisashi Doi; Kazuhiro Takahashi; Masataka Morita; Motomu Kanai; Masakatsu Shibasaki; Hiroyuki Kusuhara; Yuichi Sugiyama; Hirotaka Onoe; Yasuyoshi Watanabe, UNLABELLED: P-glycoprotein (P-gp) plays a pivotal role in limiting the penetration of xenobiotic compounds into the brain at the blood-brain barrier (BBB), where its expression increases with maturation in rats. We investigated developmental changes in P-gp function in the BBB of nonhuman primates using PET with R-(11)C-verapamil, a PET radiotracer useful for evaluating P-gp function. In addition, developmental changes in the brain penetration of (11)C-oseltamivir, a substrate for P-gp, was investigated as practical examples. METHODS: PET studies in infant (age, 9 mo), adolescent (age, 24-27 mo), and adult (age, 5.6-6.6 y) rhesus monkeys (Macaca mulatta) were performed with R-(11)C-verapamil and also with (11)C-oseltamivir. Arterial blood samples and PET images were obtained at frequent intervals up to 60 min after administration of the PET tracer. Dynamic imaging data were evaluated by integration plots using data collected within the first 2.5 min after tracer administration. RESULTS: R-(11)C-verapamil rapidly penetrated the brain, whereas the blood concentration of intact R-(11)C-verapamil decreased rapidly in all subjects. The maximum brain uptake in infant (0.033% ± 0.007% dose/g of brain) and adolescent (0.020% ± 0.002% dose/g) monkeys was 4.1- and 2.5-fold greater, respectively, than uptake in adults (0.0082% ± 0.0007% dose/g). The clearance of brain R-(11)C-verapamil uptake in adult monkeys was 0.056 ± 0.010 mL/min/g, significantly lower than that in infants (0.11 ± 0.04 mL/min/g) and adolescents (0.075 ± 0.023 mL/min/g). (11)C-oseltamivir showed little brain penetration in adult monkeys, with a clearance of R-(11)C-verapamil uptake of 0.0072 and 0.0079 mL/min/g, slightly lower than that in infant (0.0097 and 0.0104 mL/min/g) and adolescent (0.0097 and 0.0098 mL/min/g) monkeys. CONCLUSION: These results suggest that P-gp function in the BBB changes with development in rhesus monkeys, and this change may be closely related to the observed difference in drug responses in the brains of children and adult humans., Jun. 2011, 52, 6, 950, 7, Scientific journal, True
  • Refereed, Neuroreport, LIPPINCOTT WILLIAMS & WILKINS, Increase in hypothalamic aromatase in macaque monkeys treated with anabolic-androgenic steroids: PET study with [11C]vorozole., Kayo Takahashi; Kayo Onoe; Hisashi Doi; Hiroko Nagata; Gen Yamagishi; Takamitsu Hosoya; Yasuhisa Tamura; Yasuhiro Wada; Hajime Yamanaka; Chihiro Yokoyama; Hiroshi Mizuma; Tadayuki Takashima; Mats Bergström; Hirotaka Onoe; Bengt Långström; Yasuyoshi Watanabe, In an earlier study in rodents, we showed that the aromatase that converts androgens to estrogens in the preoptic area and bed nucleus of stria terminalis was significantly increased in concentration after exposure to anabolic-androgenic steroids. To confirm whether this occurs in primates, we conducted a positron emission tomographic study using macaque monkeys. Male rhesus monkeys were treated with nandrolone decanoate for 3 weeks. To measure aromatase concentrations, we performed positron emission tomographic imaging using a 11C-labeled specific aromatase inhibitor, [11C]vorozole. After treatment with nandrolone, significant increase in [11C]vorozole binding was observed in the hypothalamus but not other areas including the amygdala, which is also aromatase enriched. These findings in monkeys are consistent with those we obtained earlier in rats. These findings strongly suggest that aromatase in the hypothalamus may play a crucial role in the emotional instability of anabolic-androgenic steroids abusers., 11 May 2011, 22, 7, 326, 30, Scientific journal, True
  • Refereed, Frontiers in behavioral neuroscience, Relaxin-3-deficient mice showed slight alteration in anxiety-related behavior., Yoshihisa Watanabe; Atsushi Tsujimura; Keizo Takao; Kazunori Nishi; Yasuaki Ito; Yoshitaka Yasuhara; Yasuhito Nakatomi; Chihiro Yokoyama; Kenji Fukui; Tsuyoshi Miyakawa; Masaki Tanaka, Relaxin-3 is a neuropeptide belonging to the relaxin/insulin superfamily. Studies using rodents have revealed that relaxin-3 is predominantly expressed in neurons in the nucleus incertus (NI) of the pons, the axons of which project to forebrain regions including the hypothalamus. There is evidence that relaxin-3 is involved in several functions, including food intake and stress responses. In the present study, we generated relaxin-3 gene knockout (KO) mice and examined them using a range of behavioral tests of sensory/motor functions and emotion-related behaviors. The results revealed that relaxin-3 KO mice exhibited normal growth and appearance, and were generally indistinguishable from wild genotype littermates. There was no difference in bodyweight among genotypes until at least 28 weeks after birth. In addition, there were no significant differences between wild-type and KO mice in locomotor activity, social interaction, hot plate test performance, fear conditioning, depression-like behavior, and Y-maze test performance. However, in the elevated plus maze test, KO mice exhibited a robust increase in the tendency to enter open arms, although they exhibited normal performance in a light/dark transition test and showed no difference from wild-type mice in the time spent in central area in the open field test. On the other hand, a significant increase in the acoustic startle response was observed in KO mice. These results indicate that relaxin-3 is slightly involved in the anxiety-related behavior., 2011, 5, 50, 50, Scientific journal, True
  • Refereed, Synapse (New York, N.Y.), Mapping of serotonin transporters by positron emission tomography with [11C]DASB in conscious common marmosets: comparison with rhesus monkeys., Chihiro Yokoyama; Hajime Yamanaka; Kayo Onoe; Akihiro Kawasaki; Hiroko Nagata; Keiko Shirakami; Hisashi Doi; Hirotaka Onoe, The common marmoset (Callithrix jacchus) is unique among the primates in its small body size, reproductive efficacy, and characteristic social behavior, making it useful as an animal model in neuroscientific research. To assess the brain serotonergic systems, we investigated the binding of [(11)C]-3-amino-4-(2-dimetylaminomethyl-phenylsulfanyl)-benzonitrile ([(11)C]DASB) to brain serotonin transporter (SERT) in conscious common marmosets using positron emission tomography (PET), and compared with findings for rhesus monkeys. Both species showed globally similar distribution patterns of [(11)C]DASB uptake in the brain, with highest activity in the midline of the brain and lowest in the cerebellum, and higher activity in some subcortical regions than in surrounding cortex, while the common marmoset brain showed almost equal or rather higher binding potential (BP) values (BP(ND)) in cortical regions and hippocampus, and lower BP(ND) than the rhesus monkey brain in some subcortical regions. Test-retest reproducibility of BP(ND) at an interval of several months was high, indicating reliable and stable measurements of serotonin transporters in both species. These results suggest that SERT imaging by PET with [(11)C]DASB under conscious state is valuable for investigating the physiological serotonergic functions in common marmosets (182)., Aug. 2010, 64, 8, 594, 601, Scientific journal, True
  • Refereed, Experimental animals, Age-dependent alteration in hippocampal neurogenesis correlates with learning performance of macaque monkeys., Ken Aizawa; Naohide Ageyama; Chihiro Yokoyama; Tatsuhiro Hisatsune, Newborn neurons are continuously produced in the hippocampus, which may be involved in several cognitive functions, including learning and memory, throughout life. However, both hippocampus-dependent cognitive functions and the level of adult neurogenesis are gradually attenuated as aging progresses. Few studies have explored the relationship between adult neurogenesis and cognitive functions, especially in primates. In this study, we evaluated learning performance and hippocampal neurogenesis utilizing young and aged cynomolgus monkeys. Significant attenuations in learning performance and adult neurogenesis were detected in aged monkeys. Interestingly, there was a positive correlation between learning performance and the level of neurogenesis. Our findings suggest that cognitive functions and adult neurogenesis may have some interdependent relationships during aging., Jul. 2009, 58, 4, 403, 7, Scientific journal, False
  • Refereed, NEUROSCIENCE RESEARCH, ELSEVIER IRELAND LTD, Mapping serotonin transporters with [C-11]DASB positron emission tomography in common marmosets under conscious condition: comparison with macaque monkeys, Chihiro Yokoyama; Hajime Yamanaka; Kayo Onoe; Akihiro Kawasaki; Hiroko Nagata; Keiko Shirakami; Hisashi Doi; Yasuyoshi Watanabe; Hirotaka Onoe, 2009, 65, S227, S227
  • Refereed, Neuroscience letters, Serotonergic mediation of the antidepressant-like effect of the green leaves odor in mice., Yasuhito Nakatomi; Chihiro Yokoyama; Seijiro Kinoshita; Daiki Masaki; Hideto Tsuchida; Hirotaka Onoe; Kanji Yoshimoto; Kenji Fukui, The green odor (GO) that emanates from green leaves has been observed to have many physiological actions in mammals and may be associated with a healing effect in humans. This study examined the effect of GO (we used a mixture of cis-3-hexenol and trans-2-hexenal) on behavior in the forced swim test (FST) of depression in mice. Exposure of GO showed the antidepressant-like effect in the FST, i.e., a significant decrease in immobility time and increase in swimming time, but no change in climbing time. The behavioral responses of GO-exposed animals to FST were similar to those observed for animals given citalopram, which is a selective serotonin reuptake inhibitor. In contrast, desipramine, which is a selective noradrenaline reuptake inhibitor, decreased immobility time and increased climbing time without affecting swimming time. To examine the involvement of the serotonergic system in mediating the antidepressant-like action of GO, we performed further FST examinations in which GO-exposed mice were treated with p-chlorophenylalanine (PCPA). Prior PCPA administration induced depletion of central 5-HT in the brain and completely diminished the GO effect on the behavioral responses seen during the FST. No changes in locomotor activity after GO inhalation were observed. These results indicate that acute exposure to GO has an antidepressant-like effect that may involve the serotonergic system., 09 May 2008, 436, 2, 167, 70, Scientific journal, True
  • Refereed, Neuroscience research, ELSEVIER IRELAND LTD, Effects of rat medial prefrontal cortex lesions on olfactory serial reversal and delayed alternation tasks., Seijiro Kinoshita; Chihiro Yokoyama; Daiki Masaki; Tatsuhisa Yamashita; Hideto Tsuchida; Yasuhito Nakatomi; Kenji Fukui, When reward reinforcement in a two-choice discrimination task is regularly changed from one stimulus to another immediately after one learning acquisition session, the learning efficiency of a rat increases as if the rat has come to recognize this regularity of reversal. To investigate how the rat medial prefrontal cortex (mPFC) is involved in such improvement, we examined the performance of mPFC-lesioned rats in a serial reversal task of olfactory discrimination. The performance of other mPFC-lesioned rats in a delayed alternation task was also analyzed using the same apparatus to evaluate the contribution of the mPFC to working memory. The mPFC-lesioned rats demonstrated selective difficulty in the second reversal session in the serial reversal task and also showed performance impairment in the delayed alternation task. These results suggest that the rat mPFC mediating working memory is involved in early progress in learning efficiency during experiences of multiple reversals, which may be relevant to cognitive operations in reversal learning beyond a one-time reversal of stimulus response associations., Feb. 2008, 60, 2, 213, 8, Scientific journal, True
  • Refereed, NEUROSCIENCE RESEARCH, Increase in aromatase level by treatment of anabolic androgenic steroids in rat and rhesus monkey brain, Takahashi Kayo; Onoe Kayo; Doi Hisashi; Nagata Hiroko; Yamagishi Gen; Hosoya Takamitsu; Tamura Yasuhisa; Wada Yasuhiro; Yamanaka Hajime; Yokoyama Chihiro; Takashima Tadayuki; Bergstrom Mats; Onoe Hirotaka; Langstrom Bengt; Watanabe Yasuyoshi, 2008, 61, S271
  • Refereed, Psychopharmacology, SPRINGER, Relationship between limbic and cortical 5-HT neurotransmission and acquisition and reversal learning in a go/no-go task in rats., Daiki Masaki; Chihiro Yokoyama; Seijiro Kinoshita; Hideto Tsuchida; Yasuhito Nakatomi; Kanji Yoshimoto; Kenji Fukui, RATIONALE: Specific brain structures have been suggested to be involved in impulsive responding assessed by a variety of operant tasks. Central serotonin (5-HT) function has also been widely implicated in impulsivity; however, little research has addressed the regional aspect of 5-HT roles in different impulsive indices of task performance. OBJECTIVE: We analyzed the relationships between acquisition and reversal learning in a go/no-go task as different behavioral measures of impulsivity and focal concentrations of 5-HT and its metabolites in the brain. MATERIALS AND METHODS: Rats administered with parachloroamphetamine (PCA) and vehicle were tested in both acquisition and reversal phases in a go/no-go visual discrimination task. Neurochemical analysis was performed to determine 5-HT concentrations in micropunched brain tissues. RESULTS: PCA administration induced regionally 5-HT depletion in the brain and impaired learning performance in both tests. For both tests, significant negative correlations between learning performance and 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were observed in the medial prefrontal cortex (mPFC) and amygdala (Amyg). In contrast, significant negative correlations between learning performance and 5-HT and 5-HIAA concentrations were observed for the orbitofrontal cortex (OFC) exclusively in the reversal learning phase. CONCLUSIONS: The present data indicate that 5-HT neurotransmission to the mPFC and Amyg is involved in inhibitory control over responses to discriminated stimuli associated with the go/no-go paradigm common to both tests. In contrast, 5-HT neurotransmission to the OFC is especially involved in additional processes associated with reversal learning., Dec. 2006, 189, 2, 249, 58, Scientific journal, True
  • Refereed, Stroke, LIPPINCOTT WILLIAMS & WILKINS, Neuroprotection by a central nervous system-type prostacyclin receptor ligand demonstrated in monkeys subjected to middle cerebral artery occlusion and reperfusion: a positron emission tomography study., Yilong Cui; Hiroyuki Takamatsu; Takeharu Kakiuchi; Hiroyuki Ohba; Yosky Kataoka; Chihiro Yokoyama; Hirotaka Onoe; Yumiko Watanabe; Takamitsu Hosoya; Masaaki Suzuki; Ryoji Noyori; Hideo Tsukada; Yasuyoshi Watanabe, BACKGROUND AND PURPOSE: Recently, we found that a novel subtype of prostacyclin (PGI(2)) receptor clearly distinct from the peripheral subtype in terms of ligand specificity is expressed in the central nervous system (CNS). (15R)-16-m-tolyl-17,18,19,20-tetranorisocarbacyclin (15R-TIC) was synthesized and demonstrated to be a specific ligand for this CNS-type PGI(2) receptor. Previously, we demonstrated 15R-TIC to be neuroprotective in vivo during transient forebrain ischemia in gerbils and permanent middle cerebral artery occlusion (MCAO) in rats. Furthermore, this compound was shown to exert an anti-apoptotic effect on primary cultured hippocampal neurons, indicating its neuroprotective effect against ischemic insults occurs via direct action on CNS-type PGI(2) receptor. METHODS: Local cerebral hemodynamics and oxygen metabolism were measured simultaneously by using positron emission tomography with the (15)O steady-state method, before and up to 18 hours after 3-hour transient MCAO reperfusion in cynomolgus monkeys. Methyl ester of 15R-TIC (50 microg/kg, n=4) or its vehicle (10% Intralipos, n=4) was injected intravenously within 5 minutes after onset of MCAO and continuously infused for 5 hours (50 microg/kg per hour). RESULTS: Neuropathology showed that 15R-TIC significantly reduced cortical damage after 3-hour MCAO. Positron emission tomography results showed 15R-TIC significantly reduced the volume of "infarct" region of interest and attenuated the decrease in cerebral metabolic rate of oxygen and oxygen extraction fraction, and these protective effects were not attributable to improvement of cerebral circulation. CONCLUSIONS: These results suggest that 15R-TIC has a potent neuroprotective effect against focal cerebral ischemia in a monkey MCAO via its direct action on CNS-type PGI(2) receptors., Nov. 2006, 37, 11, 2830, 6, Scientific journal, True
  • Refereed, Progress in neuro-psychopharmacology & biological psychiatry, Regional cerebral blood flow changes associated with interoceptive awareness in the recovery process of anorexia nervosa., Ryohei Matsumoto; Yurinosuke Kitabayashi; Jin Narumoto; Yoshihisa Wada; Akiko Okamoto; Yo Ushijima; Chihiro Yokoyama; Tatsuhisa Yamashita; Hidehiko Takahashi; Fumihiko Yasuno; Tetsuya Suhara; Kenji Fukui, BACKGROUND: An abnormality in regional cerebral blood flow (rCBF) in anorexia nervosa (AN) patients has been reported. There are very few studies that have investigated the rCBF changes in the recovery process of AN. METHODS: For eight female AN patients, we performed (123)I-IMP single photon emission computed tomography (SPECT) and four psychological assessments (Eating Disorder Inventory (EDI), Eating Attitude Test (EAT), Self-Rating Depression Scale (SDS) and State-Trait Anxiety Inventory (STAI)) both before and after inpatient-behavioral therapy. SPECT images were analyzed using statistical parametric mapping software. We also performed correlational analysis between rCBF and clinical variables. RESULTS: Following treatment, the patients showed significant body weight recovery. They showed significant improvement in EAT, SDS, STAI and a subscale of EDI - interoceptive awareness (IA) - but not in total EDI or other EDI subscales. Significant rCBF increases were observed in the precuneus, posterior cingulate cortex (PCC), right dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC) and medial prefrontal cortex (MPFC) by the treatment. Significant correlation was observed between rCBF of right DLPFC and IA score before treatment. CONCLUSIONS: Changes of rCBF in right DLPFC, ACC, MPFC, PCC and precuneus were related to the AN recovery process and might be associated with improvement of IA following treatment., 30 Sep. 2006, 30, 7, 1265, 70, Scientific journal, True
  • Refereed, Cerebral cortex (New York, N.Y. : 1991), OXFORD UNIV PRESS INC, A dynamic shift of neural network activity before and after learning-set formation., Chihiro Yokoyama; Hideo Tsukada; Yasuyoshi Watanabe; Hirotaka Onoe, Learning-set (LS) is a property of insight and hypothesis testing characterized by the ability to solve novel problems based on previous experiences with problem solving. However, the neural organization and mechanisms underlying LS remain unclear. To further characterize this process, positron emission tomography (PET) studies with [15O]H2O were performed to measure regional cerebral blood flow (rCBF) during the learning phase of the two-choice visual discrimination task under the LS paradigm in rhesus monkeys. When comparing studies before and after LS formation, the orbitofrontal and lateral prefrontal cortices were differentially activated, and functional connections between these structures and the striatum, which contributes to habit learning, were altered. We conclude that changes in the lateral prefrontal cortex during problem solving may contribute to the executive function of working memory and also inhibit control of a primitive learning system, thereby promoting LS formation., Jun. 2005, 15, 6, 796, 801, Scientific journal, True
  • Refereed, The Tohoku journal of experimental medicine, TOHOKU UNIV MEDICAL PRESS, Effects of ethanol on the induction of uncoupling protein-1 (UCP1) mRNA in the mouse brown adipose tissue., Kanji Yoshimoto; Masahiro Yasuhara; Setsuo Komura; Yuki Misumi; Yuki Uchiyama; Akinori Kogure; Chizuko Hioki; Yasuo Wakabayashi; Yoshiko Satomi; Akira Nishimura; Fumihiko Fukuda; Masafumi Hori; Chihiro Yokoyama; Toshihide Yoshida, Expression of uncoupling protein-1 (UCP1) is increased by cold acclimation and overfeeding, and reduced in fasting and genetic obesity. It is known that the mitochondrial UCP1 in the brown adipose tissue (BAT) is an important key molecule for non-shivering thermogenesis. On the other hand, ethanol (EtOH) alters thermoregulation in humans and laboratory animals. However, the relationship between EtOH intake and UCP1 expression is not yet clear. Accordingly, the present study employed the technique of real-time quantitative polymerase-chain reaction (PCR) to investigate the effects of EtOH (0.5 or 2.0 g/kg) on the expression of UCP1 mRNA in the mouse BAT. Control mice were injected with the same volume of physiological saline intraperitoneally (IP). IP injection of EtOH (0.5 g/kg) caused a decrease and an increase of the expression of BAT UCP1 mRNA at 1 and 4 hours, respectively. Treatment with EtOH (2.0 g/kg) caused an increases of the expression of BAT UCP1 mRNA at both 2 and 4 hours. BAT UCP1 mRNA levels in both groups increased at 4 hours after EtOH administration. The levels of UCP1 mRNA returned to the control levels by 8 hours after EtOH administration. The expression of BAT UCP1 mRNA was upregulated following EtOH administration, although a lower dose of EtOH initially reduced the expression of UCP1 mRNA in BAT. These findings suggest that EtOH-induced UCP1 mRNA expression in BAT reflects an alteration of the set point of thermogenesis., Sep. 2004, 204, 1, 45, 51, Scientific journal, False
  • Refereed, Behavioural brain research, ELSEVIER SCIENCE BV, Increase in reaction time for solving problems during learning-set formation., Chihiro Yokoyama; Hirotaka Onoe; Yasuyoshi Watanabe, Six rhesus monkeys were tested for a change in reaction time for problem-solving during a learning-set task, in which they showed progressive improvement in the rate of learning successive problems of visual discrimination. To evaluate the processing time for cognitive processes in problem-solving, the differences in release latency and movement time between the visual discrimination task and the visuomotor control task were defined. In their first experience, the monkeys required several hundreds of trials for solving the problem, and the Deltarelease latency was constant throughout the learning. With increasing experience, they solved problems within fewer trials than with the first problem. At this stage, the Deltarelease latency was high at the beginning and then decreased. The rise in the Deltarelease latency within the learning acquisition period increased depending on the amount of experience with problems they had solved, whereas the Deltamovement time within that period was not significantly affected by the experience with problems. The present findings suggest that the number of problem-solving experiences could promote profound cognitive processing, which may be related to a conceptual representation that actualizes the flexibility of learning, namely, the learning set., 09 Jul. 2004, 152, 2, 221, 9, Scientific journal, True
  • Refereed, Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology, [Non-human primate behaviors as models for development of higher cognitive functions]., Chihiro Yokoyama; Hirotaka Onoe; Kayo Onoe; Hideo Tsukada; Yasuyoshi Watanabe; Kenji Fukui, Non-human primate behaviors have a special value for the neurobiological study of the development of higher cognitive functions of humans, because of the near evolutional relation between two species. We surveyed results and futures of neurobiological studies of a retrieval task, a learning-set and a self-injurious behavior expressed by non-human primates. On the retrieval task that is related to the development of inhibitory control, it was revealed a hierarchical ordering of inhibitory control processes in which the distinct neuronal circuits were involved. On the learning-set that is related to the development of abstract thinking, neural circuits for the individual learning dramatically changed from an automatic process to a cognitive process depending on the learning-set formation. The self-injurious behavior is expressed during early normal development in humans, and no other animals but non-human primates express it without administration of drugs. For that behavior, probable change in interactions of multiple monoaminergic systems was suggested as its underlying causes. Further studies on development of higher cognitive functions using non-human primates could be required for understanding the nature of human cognition., Feb. 2003, 23, 1, 1, 9, Scientific journal, False
  • Refereed, Biochemical and biophysical research communications, ACADEMIC PRESS INC ELSEVIER SCIENCE, Targeted tissue oxidation in the cerebral cortex induces local prolonged depolarization and cortical spreading depression in the rat brain., Yilong Cui; Yosky Kataoka; Qing Hua Li; Chihiro Yokoyama; Aya Yamagata; Noriko Mochizuki-Oda; Jun Watanabe; Hisao Yamada; Yasuyoshi Watanabe, Spreading depression (SD) has been linked to several neurological disorders as epilepsy, migraine aura, trauma, and cerebral ischemia, which were also influenced by disorderliness of the brain redox homeostasis. To investigate whether local tissue oxidation directly induces SD, we oxidized a restricted local area of the rat cerebral cortex using photo-dynamic tissue oxidation (PDTO) technique and examined the cerebral blood flow (CBF) and direct current (DC) potential in and around the oxidized area. Intensive PDTO induced prolonged depolarization only in the photo-oxidized area, which led to global changes of CBF and DC potential: synchronous negative shifts of DC potential (with an amplitude of approximately 20 mV) and hyperperfusion of CBF occurred. The changes in DC potential and CBF spread at a rate of around 3mm/min beyond the oxidized area to the whole hemisphere of the cerebral cortex, indicating that intensive local oxidation induces SD in the rat brain., 17 Jan. 2003, 300, 3, 631, 6, Scientific journal, True
  • Refereed, Ryoikibetsu shokogun shirizu, [Somatogenic depression (mood disorder)]., Hideto Tsuchida; Chihiro Yokoyama; Yusuke Kishikawa; Kenji Fukui, 2003, 38, 292, 5, Scientific journal, False
  • Refereed, Ryoikibetsu shokogun shirizu, [Enzyme deficiency (disorders of amino acid metabolism, disorders of lipid metabolism)]., Hideto Tsuchida; Yurinosuke Kitabayashi; Chifuyu Yamada; Chihiro Yokoyama; Kenji Fukui, 2003, 40, 383, 6, Scientific journal, False
  • Refereed, NeuroImage, ACADEMIC PRESS INC ELSEVIER SCIENCE, Neural substrates of human facial expression of pleasant emotion induced by comic films: a PET Study., Masao Iwase; Yasuomi Ouchi; Hiroyuki Okada; Chihiro Yokoyama; Shuji Nobezawa; Etsuji Yoshikawa; Hideo Tsukada; Masaki Takeda; Ko Yamashita; Masatoshi Takeda; Kouzi Yamaguti; Hirohiko Kuratsune; Akira Shimizu; Yasuyoshi Watanabe, Laughter or smile is one of the emotional expressions of pleasantness with characteristic contraction of the facial muscles, of which the neural substrate remains to be explored. This currently described study is the first to investigate the generation of human facial expression of pleasant emotion using positron emission tomography and H(2)(15)O. Regional cerebral blood flow (rCBF) during laughter/smile induced by visual comics and the magnitude of laughter/smile indicated significant correlation in the bilateral supplementary motor area (SMA) and left putamen (P < 0.05, corrected), but no correlation in the primary motor area (M1). In the voluntary facial movement, significant correlation between rCBF and the magnitude of EMG was found in the face area of bilateral M1 and the SMA (P < 0.001, uncorrected). Laughter/smile, as opposed to voluntary movement, activated the visual association areas, left anterior temporal cortex, left uncus, and orbitofrontal and medial prefrontal cortices (P < 0.05, corrected), whereas voluntary facial movement generated by mimicking a laughing/smiling face activated the face area of the left M1 and bilateral SMA, compared with laughter/smile (P < 0.05, corrected). We demonstrated distinct neural substrates of emotional and volitional facial expression and defined cognitive and experiential processes of a pleasant emotion, laughter/smile., Oct. 2002, 17, 2, 758, 68, Scientific journal, True
  • Refereed, Genes to cells : devoted to molecular & cellular mechanisms, BLACKWELL PUBLISHING LTD, Circadian rhythm of aromatic L-amino acid decarboxylase in the rat suprachiasmatic nucleus: gene expression and decarboxylating activity in clock oscillating cells., Yoshiki Ishida; Chihiro Yokoyama; Tsutomu Inatomi; Kazuhiro Yagita; Xin Dong; Lily Yan; Shun Yamaguchi; Ikuko Nagatsu; Takahide Komori; Kunio Kitahama; Hitoshi Okamura, BACKGROUND: Aromatic L-amino acid decarboxylase (AADC) is the enzyme responsible for the decarboxylation step in both the catecholamine and indoleamine synthetic pathways. In the brain, however, a group of AADC containing neurones is found outside the classical monoaminergic cell groups. Since such non-monoaminergic AADC is expressed abundantly in the suprachiasmatic nucleus (SCN), the mammalian circadian centre, we characterized the role of AADC in circadian oscillation. RESULTS: AADC gene expression was observed in neurones of the dorsomedial subdivision of the SCN and its dorsal continuant in the anterior hypothalamic area. These AADC neurones could uptake exogenously applied L-DOPA and formed dopamine. AADC was co-expressed with vasopressin and the clock gene Per1 in the neurones of the SCN. Circadian gene expression of AADC was observed with a peak at subjective day and a trough at subjective night. The circadian rhythm of AADC enzyme activity in the SCN reflects the expression of the gene. CONCLUSIONS: Non-monoaminergic AADC in the SCN is expressed in clock oscillating cells, and the decarboxylating activity of master clock cells are under the control of the circadian rhythm., May 2002, 7, 5, 447, 59, Scientific journal, True
  • Refereed, Neuroscience, Elsevier BV, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine reduces intracellular calcium response to noradrenaline in rat visual cortex, M Yamamoto; K Imamura; M Kobayashi; K Nakadate; C Yokoyama; Y Watanabe; Mi Yamamoto; A Negi, Nov. 2001, 107, 2, 209, 218, Scientific journal
  • 神経化学, 日本神経化学会, PET試行時の疲労評価, 田島 世貴; 山本 茂幸; 岩瀬 真生; 梶本 修身; 吉川 悦次; 尾上 浩隆; 横山 ちひろ; 岡田 裕之; 中村 夫左央; 塚田 秀夫, Sep. 2001, 40, 2-3, 402, 402
  • 神経化学, 日本神経化学会, H2^15O-PETによるヒトの笑いと随意顔面運動の比較, 岩瀬 真生; 尾内 康臣; 岡田 裕之; 横山 ちひろ; 延澤 秀二; 吉川 悦次; 塚田 秀夫; 竹田 真己; 山下 仰; 武田 雅俊, Sep. 2001, 40, 2-3, 402, 402
  • Refereed, Brain Research, Elsevier BV, Regional expressions of Fos-like immunoreactivity in rat cerebral cortex after stress; restraint and intraperitoneal lipopolysaccharide, Chihiro Yokoyama; Kazunobu Sasaki, Jan. 1999, 816, 2, 267, 275, Scientific journal
  • Refereed, J Pharmacol Exp Ther, Self-injurious behavior and dopaminergic neuron system in neonatal 6-hydroxydopamine-lesioned rat: 2. Intracerebral microinjection of dopamine agonists and antagonists, H Okamura; T Murakami; C Yokoyama; T Nakamura; Y Ibata, Feb. 1997, 280, 2, 1031, 1037
  • Refereed, J Pharmacol Exp Ther . 1997 Feb;280(2):1016-30., Self-injurious behavior and dopaminergic neuron system in neonatal 6-hydroxydopamine-lesioned rat: 1. Dopaminergic neurons and receptors, C Yokoyama; H Okamura, Feb. 1997, 280, 2, 1016, 1030
  • Refereed, Cells Tissues Organs, S. Karger AG, Mitochondrial Density of Ventral Horn Neurons in the Rat Spinal Cord, A. Ishihara; S. Hayashi; R.R. Roy; Y. Yamada; C. Yokoyama; Y. Ohira; V.R. Edgertone; Y. Ibata, 1997, 160, 4, 248, 253, Scientific journal
  • Refereed, Experimental Neurology, Elsevier BV, Lateromedial Gradient of the Susceptibility of Midbrain Dopaminergic Neurons to Neonatal 6-Hydroxydopamine Toxicity, Hitoshi Okamura; Chihiro Yokoyama; Yasuhiko Ibata, Dec. 1995, 136, 2, 136, 142, Scientific journal
  • Refereed, Brain Research, Elsevier BV, Dopamine D2-like receptors labeled by [3H]YM-09151-2 in the rat hippocampus: characterization and autoradiographic distribution, Chihiro Yokoyama; Hitoshi Okamura; Yasuhiko Ibata, May 1995, 681, 1-2, 153, 159, Scientific journal
  • Refereed, The Journal of Comparative Neurology, Wiley, Autoradiographic distribution of [3H]YM-09151-2, a high-affinity and selective antagonist ligand for the dopamine D2 receptor group, in the rat brain and spinal cord, Chihiro Yokoyama; Hitoshi Okamura; Teruo Nakajima; Jun-Ichi Taguchi; Yasuhiko Ibata, 01 Jun. 1994, 344, 1, 121, 136, Scientific journal
  • Refereed, Brain Research Bulletin, Elsevier BV, Resistance of hypothalamic dopaminergic neurons to neonatal 6-hydroxydopamine toxicity, Chihiro Yokoyama; Hitoshi Okamura; Yasuhiko Ibata, Jan. 1993, 30, 5-6, 551, 559, Scientific journal


  • Not Refereed, 2022, 68, 2, 15, 20
  • 精神医学, マーモセットの社会認知とニューロイメージング, 横山ちひろ, 2016, 58, 1, 15, 21
  • 臨床神経科学, 動物モデルとしてのマーモセットの展望, 2014, 32, 952, 953
  • Not Refereed, 臨床放射線, 金原出版(株), 【脳疾患における分子イメージング】 分子イメージングによるトランスレーショナルリサーチ 創薬と病態科学のための分子イメージング, 水間 広; 横山 ちひろ; 宿里 充穂; 山中 創; 尾上 浩隆, Apr. 2010, 55, 4, 509, 516
  • 脳と精神の医学, 物質乱用における脳機能画像研究の進歩, 北林百合之介; 上田英樹; 横山ちひろ; 福居顯二, 2004, 14, 4, 299, 303
  • 脳と精神の医学, 京都府立医科大学における生物学的精神医学研究, 横山ちひろ; 北林百合之介; 土田英人; 國澤正寛; 岡本明子; 福居顯二, 2004, 15, 3, 345, 352
  • Clinical Neuroscience, 薬物依存の組織化学所見, 土田英人; 北林百合之介; 横山ちひろ; 福居顯二, 2004, 22, 6, 651, 655
  • 日本医師会雑誌『精神障害の臨床』別刷, アルコール・覚せい剤などの薬物乱用, 北林百合之介; 横山ちひろ; 福居顯二, 2004, 131, 12, S192, S193
  • アルコール精神医学雑誌, 症例からみた薬物依存のニューロイメージング, 北林百合之介; 横山ちひろ; 福居顯二, 2004, 11, 1, 57, 62
  • Not Refereed, 日本臨床, (株)日本臨床社, 【精神医学症候群 器質・症状性精神障害など】 症状精神病 酵素欠陥症(アミノ酸代謝障害、脂質代謝障害), 土田 英人; 北林 百合之介; 山田 千冬; 横山 ちひろ; 福居 顯二, Oct. 2003, 別冊, 精神医学症候群III, 383, 386
  • Pharma Medica, うつ病の薬物療法-三環系, 四環系抗うつ薬を中心に-, 北林百合之介; 土田英人; 横山ちひろ; 福居顕二, 2002, 20, 3, 47, 52
  • 総合臨床, 過度の潔癖傾向, 吉田卓史; 横山ちひろ; 福居顕二, 2002, 51, 5, 946, 950
  • 脳と精神の医学, 自傷行為とドーパミン神経系, 岡村均; 横山ちひろ, 1993, 4, 491, 496
  • 脳と精神の医学, メタンフェタミンのマウス黒質線条体ドーパミン神経系への影響−チロシン水酸化酵素免疫組織化学法を用いて, 福居顕二; 飯住英幸; 松本好剛; 横山ちひろ; 凝地浩彦; 三宅雅人; 川上富美郎; 中嶋照夫, 1991, 2, 589, 594
  • Not Refereed, Psychiatry, Family and brain evolution, Chihiro Yokoyama, Nov. 2021, 39, 5, 515, 521, Introduction scientific journal

Books etc

  • Genes to Animal Behavior, Springer, Yokoyama C; Onoe H, Molecular brain imaging of personality traits in nonhuman primates: A study of the common marmoset., 2011
  • Emotion, Memory and Behavior., Japan Scientific Societies Press, Okamura H; Yokoyama C, Self-mutilation behavior and brain dopaminergic neuron system in neonatal 6-hydroxydopamine lesioned rat, 1994


  • Chihiro Yokoyama; Kazuhide Hashiya; Xianwei Meng; Hiromi Kobayashi; Miho Inoue-murayama; Chiho Takeda; Akihiro Kawasaki; Takuya Hayashi, 日本人間行動進化学会第13回大会, Behavioral assessment of communicative responding to human’s direct gaze in live situation in macaque monkeys, Oral presentation, 12 Dec. 2020
  • Chihiro Yokoyama, 第43回日本神経科学学会, Brain connectome underlying sociability in nonhuman primates, 29 Jul. 2020
  • 横山ちひろ, 2019年度⽣理研研究会『視覚・認知脳機能研究の先端』, 非ヒト霊長類脳機能イメージング―社会的認知機能の起源を探る―, 07 Sep. 2019
  • Takayuki Ose; Joonas Autio; Masataka Ohno; Akihiro Kawasaki; Chiho Takeda; Yuki Hori; Kantaro Nishigori; Tomokazu Nakako; Chihiro Yokoyama; Hidetaka Nagata; Tetsuo Yamamori; Hiroshi Watabe; Takuya Hayashi, 第9回日本マーモセット研究会大会, The development of maker-based localization system, estimation of individual brain variability, 14 Feb. 2019
  • Chiho Takeda; Akihiro Kawasaki; Chihiro Yokoyama; Takuya Hayashi, マーモセット育成管理の工夫:補助飼料と補助ミルクの活用例, 14 Feb. 2019
  • Chihiro Yokoyama; Yuki Hori; Akihiro Kawasaki; Chiho Takeda; Alexander Weiss; Miho Inoue-murayama; Takuya Hayashi, 第9回日本マーモセット研究会, Surface-based structures by HCP-style MRI imaging and personality rating in the marmoset, 14 Feb. 2019
  • 横山ちひろ, 第2回ヒト脳イメージング研究会, 非ヒト霊長類脳分子コネクトーム解析の試み 脳-行動関連の種間比較を目指して, 07 Sep. 2018
  • 横山ちひろ, 2018年度⽣理研研究会『社会神経科学的アプローチによる精神疾患の社会性障害の理解』, 霊⻑類脳イメージングによるヒト社会性のなりたちとその障害の理解, 07 Sep. 2018
  • 竹本篤史; 高司雅史; 横山ちひろ; 渡我部昭哉; 水上浩明; 小澤敬也; 尾上浩隆; 山森哲雄; 中村克樹, 第6回日本マーモセット研究会大会, Behavioral change caused by reducing dopamine D2 receptor mRNA expression in the caudate nucleus of the common marmoset, Dec. 2016, Dec. 2016, Dec. 2016
  • 山中 創; 横山 ちひろ; 水間 広; 大野 正裕; 武田 千穂; 森 智子; 土居 久志; 尾上 浩隆, 日本疲労学会誌, ケタミンの抗うつ作用メカニズムに側坐核と腹側淡蒼球のセロトニン1Bレセプターが関与する可能性, May 2014, May 2014, May 2014, 日本疲労学会
  • 山中 創; 横山 ちひろ; 水間 広; 大野 正裕; 武田 千穂; 森 智子; Finnema Sjoerd J.; Halldin Christer; 土居 久志; 尾上 浩隆, JSMI Report, ケタミンの抗うつ作用メカニズムに側坐核と腹側淡蒼球のセロトニン1Bレセプターが関与する可能性 マカクザルを用いたPET研究, May 2014, May 2014, May 2014, 日本分子イメージング学会
  • Chihiro Yokoyama, 東京都医学研究所国際シンポジウムMARMOSET NEUROSCIENCE-ANATOMY, DEVELOPMENT AND FUNCTION, Imaging the ‘Social Brain’ in Common Marmosets, 04 Oct. 2013
  • 山中 創; 大野 正裕; 森 智子; 武田 千穂; 平尾 有日子; 安藤 亜美; 横山 ちひろ; 土居 久志; 尾上 浩隆, JSMI Report, 麻酔薬の[11C]DASB結合能に対する影響 マカクザルを用いた検討, May 2012, May 2012, May 2012, 日本分子イメージング学会
  • 横山 ちひろ; 川崎 章弘; 高橋 佳代; 細谷 孝充; 渡辺 恭良; 尾上 浩隆, JSMI Report, 脳内アロマテース活性とコモンマーモセットの社会行動特性との関連 11C-cetrozoleを用いたPET研究, May 2011, May 2011, May 2011, 日本分子イメージング学会
  • 山中 創; 横山 ちひろ; 大野 正裕; 武田 千穂; 平尾 有日子; 倉井 佐知; 土居 久志; 尾上 浩隆, JSMI Report, 無麻酔下アカゲザルのセロトニン1Bレセプターイメージング [11C]AZ10419369を用いたPET研究, May 2011, May 2011, May 2011, 日本分子イメージング学会
  • 中澤 俊介; 西村 直浩; 横山 ちひろ; 川崎 章弘; 倉井 佐知; 土居 久志; 矢野 恒夫; 渡辺 恭良; 尾上 浩隆, JSMI Report, 無麻酔下コモンマーモセットPETを用いた抗精神病薬ルラシドンとオランザピンのドパミンD2受容体占有率の評価, May 2011, May 2011, May 2011, 日本分子イメージング学会
  • Kazunori Adachi; Masayuki Kobayashi; Toshiyuki Kawasaki; Chihiro Yokoyama; Hiroshi Sakagami; Hirotaka Onoe; Noriaki Koshikawa, JOURNAL OF PHARMACOLOGICAL SCIENCES, Rhythmical masticatory movement profile in hemi-parkinsonian monkey: model of orofacial movement disorder, 2011, 2011, 2011, JAPANESE PHARMACOLOGICAL SOC, url
  • Chihiro Yokoyama; Akihiro Kawasaki; Takuya Hayashi; Hirotaka Onoe, NEUROSCIENCE RESEARCH, Neural correlates of individual responses to the presence of an unfamiliar other: C-11-DASB and F-18-FDG PET studies of marmoset monkeys, 2011, 2011, 2011, ELSEVIER IRELAND LTD, doi
  • Kazuo Hikosaka; Fumie Nanba; Chihiro Yokoyama; Hirotaka Onoe, NEUROSCIENCE RESEARCH, Performance of Go-Nogo task using voice stimuli in the common marmoset, 2011, 2011, 2011, ELSEVIER IRELAND LTD, doi
  • YOKOYAMA CHIHIRO; KAWASAKI AKIHIRO; ONOE KAYO; ONOE HIROTAKA, 神経化学, Functional relationship between monoamine transporters and traits of social behavior: A positron emission tomography study in the common marmoset, 01 Aug. 2010, 01 Aug. 2010, 01 Aug. 2010, url
  • 山中 創; 尾上 嘉代; 横山 ちひろ; 尾上 浩隆, 神経化学, プロポフォール麻酔は[11C]DASBのセロトニントランスポーターへの結合を上昇させる マカクザルを用いたPET研究(Propofol anesthesia increases the binding of [11C] DASB to serotonin transporter: PET study with macaque monkeys), Aug. 2010, Aug. 2010, Aug. 2010, 日本神経化学会, url
  • 山中 創; 尾上 嘉代; 横山 ちひろ; 尾上 浩隆, 神経化学, プロポフォール麻酔は[11C]DASBのセロトニントランスポーターへの結合を上昇させる マカクザルを用いたPET研究(Propofol anesthesia increases the binding of [11C] DASB to serotonin transporter: PET study with macaque monkeys), Aug. 2010, Aug. 2010, Aug. 2010, 日本神経化学会
  • 横山 ちひろ; 川崎 章弘; 尾上 嘉代; 尾上 浩隆, 神経化学, 社会行動特性と脳内モノアミントランスポーターとの機能的関連 コモンマーモセットを用いたPET研究(Functional relationship between monoamine transporters and traits of social behavior: A positron emission tomography study in the common marmoset), Aug. 2010, Aug. 2010, Aug. 2010, 日本神経化学会
  • Chihiro Yokoyama; Akihiro Kawasaki; Kayo Onoe; Hirotaka Onoe, NEUROSCIENCE RESEARCH, Functional relationship between monoamine transporters and traits of social behavior: A positron emission tomography study in the common marmoset, 2010, 2010, 2010, ELSEVIER IRELAND LTD, doi
  • 横山 ちひろ; 川崎 章弘; 尾上 嘉代; 長田 浩子; 畑中 恵子; 土居 久志; 尾上 浩隆, 神経化学, [11C]DASBを用いた無麻酔下マーモセット脳におけるセロトニントランスポーターのPETイメージング(Brain serotonin transporter imaging by PET with [11C] DASB in conscious marmosets), Aug. 2008, Aug. 2008, Aug. 2008, 日本神経化学会
  • Kanji Yoshimoto; Masaki Tanaka; Yoshihisa Watanabe; Chihiro Yokoyama; Akira Nishimura; Masaaki Sakabe; Hideaki Kato; Shuichi Ueda, NEUROSCIENCE RESEARCH, Serotonin2c receptor agonist, mCPP, increases voluntary alcohol drinking behavior, 2008, 2008, 2008, ELSEVIER IRELAND LTD
  • Chihiro Yokoyama; Akihiro Kawasaki; Hirotaka Onoe, NEUROSCIENCE RESEARCH, Effects of early parental privation on a primate vocal behavior: Response of the virtual confrontation test in common marmosets, 2008, 2008, 2008, ELSEVIER IRELAND LTD
  • 昌子 浩登; 中富 康仁; 横山 ちひろ; 福居 顕二; 花井 一光, 生物物理, コカイン投与マウスのロコモータ活性の解析(The Characteristics of the locomotor activity in cocaine-applied mice), Nov. 2007, Nov. 2007, Nov. 2007, (一社)日本生物物理学会
  • 横山 ちひろ, 日本薬理学雑誌, マカクサルを用いたPET脳賦活実験による神経ネットワークの解析, Sep. 2007, Sep. 2007, Sep. 2007, (公社)日本薬理学会
  • 横山ちひろ, 第116回日本薬理学界関東部会 シンポジウム『非侵襲的脳機能イメージング法による高次脳機能の探索』, マカクサルを用いたPET脳賦活実験による神経ネットワークの解析, 02 Jun. 2007
  • Yasuhito Nakatomi; Chihiro Yokoyama; Seijiro Kinoshita; Daiki Masaki; Hideto Tsuchida; Hirotaka Onoe; Kanji Yoshimoto; Kenji Fukui, NEUROSCIENCE RESEARCH, Antidepressant-like effect of green odor in mice, 2007, 2007, 2007, ELSEVIER IRELAND LTD
  • Daiki Masaki; Chihiro Yokoyama; Seijiro Kinoshita; Hideto Tsuchida; Tatsuhisa Yamashita; Yasuhito Nakatomi; Kanji Yoshimoto; Kenji Fukui, NEUROSCIENCE RESEARCH, Topographical relationships between 5-HT neurotransmission and learning performance as indices of impulsivity assessed by simple and reversal go/no-go tasks, 2006, 2006, 2006, ELSEVIER IRELAND LTD
  • Hajime Yamanaka; Kayo Onoe; Chihiro Yokoyama; Hirotaka Onoe, NEUROSCIENCE RESEARCH, Propofol anesthesia increases the binding of [C-11]DASB to serotonin transporter: PET study with macaque monkeys, 2010, 2010, 2010, ELSEVIER IRELAND LTD, doi
  • SHOJI HIROTO; NAKATOMI YASUHITO; YOKOYAMA CHIHIRO; MASAKI DAIKI; FUKUI KENJI; HANAI KAZUMITSU, 生物物理, New index for a behavioral differentiation across psychomotor stimulants, 20 Sep. 2009, 20 Sep. 2009, 20 Sep. 2009, url
  • 横山ちひろ, 学術変革領域研究B心脳限界夏の班会議, 社会性の表裏 社会性の分子・神経回路・進化, Nominated symposium, 05 Aug. 2021, rm:research_project_id

Research Projects

  • Grant-in-Aid for Scientific Research (C), 01 Apr. 2018, 31 Mar. 2021, 18K06372, Evolution of personality and individual difference : a comparative primate neuroimaging study, 横山 ちひろ, Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Institute of Physical and Chemical Research, 4420000, 3400000, 1020000, 性格(パーソナリティ)とは個人を特徴づける持続的で一貫した行動傾向であり、ヒト以外の動物界にも広く認められる。このような行動傾向の多様性は、近年の脳機能イメージング研究によって脳の構造的特徴や機能的結合の多様性に還元できることがわかってきた。本研究は、ヒトに近縁な霊長類のなかでも親和的社会性の高いコモンマーモセットのパーソナリティを抽出し、脳機能イメージングにより構造的特徴や機能的結合に還元し、ヒトの結果と比較して進化的意義について考察することを目的とする。 本年度は、前年度すでに取得した50頭のコモンマーモセットにつき、ヒトのパーソナリティおよび社会行動や意思決定を制御するとされているセロトニンおよびドーパミン神経系を標的にしたPET画像、高解像度の脳構造および安静時機能MRI画像を用いて、ヒト脳画像処理パイプラインのパラメーター設定をマーモセット脳画像に最適化し、皮質構造、安静時MRIによるコネクトーム抽出、PETによる神経伝達物質効率の定量化などの画像処理を進めた。また、前年度までに取得した77頭のコモンマーモセットの質問紙評定法による性格評定に、51頭分を追加し、合計128頭分のデータより解析した探索的因子分析により、これまでの3因子(優越的、社交的、神経質)に加えて開放性、衝動性というパーソナリティ5因子を抽出した。これら5因子は他の施設で行われた同様の手法を用いた性格評定の結果と一致する。社交的、優越的(負の負荷量)、衝動性(負の負荷量)の三者、開放性、神経質(負の負荷量)の2者はそれぞれ強い関連性をもち、このことは高次の2因子(向社会性、豪胆)の存在を示す。またセロトニン1a受容体のSNP多型を新たに発見したが、新たに抽出されたパーソナリティ因子得点との有意な関連性は認められなかった。, rm:misc;rm:presentations
  • Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), 01 Apr. 2018, 31 Mar. 2020, 18H05090, Brain mechanisms of prosociality as a pre-linguistic competence in non-human primates, 横山 ちひろ, Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area), Institute of Physical and Chemical Research, 3900000, 3000000, 900000, ヒトの言語の特徴は、階層性と意図共有による共創的なコミュニケーションにあると考えられている。動物のもつそれらに関連する萌芽的能力の神経科学基盤を明らかにすることは、ヒト言語の独自性や生物進化的な連続性の実証的知見につながる。小型霊長類の一種であるコモンマーモセットの示す向社会性の一つである利他行動は対象が広く自発的であるという他の霊長類にない特徴をもち、ヒトの発達段階初期に発現する利他行動に最も近い。ヒトの脳機能イメージング研究から、ヒト成人の向社会性には外在する誘因としての利己的動機と内在する信頼や同情からの利他的動機が存在し、それぞれ別の神経基盤が関与していることが明らかとなっている。本研究の目的は、マーモセットの自発的な向社会行動を支える神経回路を探索することにある。そのために、マーモセット向社会行動の基礎的検討およびヒトMRI脳画像解析パイプラインをマーモセット脳に最適化する技術基盤の構築を行った。向社会行動評価においては、可視隣接する2台のオペラント課題ケージを用いて、♂♀ペア8頭の初期訓練とそのうち2頭の3図形選択による向社会性課題を実施し、自己報酬選択率の上昇と他者報酬選択率の減少、およびそれぞれの学習曲線に個体差を確認した。並行してマーモセットMRI脳画像のヒト脳画像処理パイプラインへの最適化技術に基づいて各個体のMRI脳画像処理を進めた。今後向社会性課題における学習行動の数理モデルによる定量評価を行い、これらを予測因子とした脳画像統計解析によって向社会性に関連した皮質構造や機能的結合を抽出する予定である。, rm:misc
  • 新学術領域研究(研究領域提案型), 01 Apr. 2016, 31 Mar. 2018, 16H01493, ニューロイメージングからみたマーモセットが示す親和的社会行動の分子神経基盤, 横山 ちひろ, 日本学術振興会, 科学研究費助成事業 新学術領域研究(研究領域提案型), 国立研究開発法人理化学研究所, 9490000, 7300000, 2190000, 本研究の目的は、ヒトと進化的に近縁でかつ類似の社会構造をもつ非ヒト霊長類であるマーモセットの示す親和的社会行動の分子神経基盤を明らかにすることである。そのためにマーモセットの示す親和的な社会行動の客観的評価を行い、親和的社会行動に関連する脳の大域的特徴を機能的ネットワークとして抽出する脳機能イメージング技術基盤を確立する。 Ⅰ.親和的社会行動の評価 親和的社会行動の客観的評価のために構築したテレメトリーシステムを用いた血圧変動に関するデータ解析を行った。また、社会性オペラント課題を実施するためにTWINケージを用いてタッチスクリーンおよび液体報酬による反応課題訓練を行った。 Ⅱ.脳機能イメージング マーモセット高解像度MRI脳画像(解剖画像、安静時機能画像)について、ヒト用脳画像処理パイプラインに準じた脳画像処理パイプラインの構築を進め、パイプラインを利用したドーパミン、セロトニン神経系の選択的トレーサーを用いたPET脳画像の皮質マッピングを実施した。新規PETトレーサーであるオキシトシン受容体選択的PETトレーサーの開発・評価を行い、当該PETトレーサーによるマーモセット脳PET画像を取得した。
  • Grant-in-Aid for Scientific Research (B), 01 Apr. 2013, 31 Mar. 2017, 25293254, Principal investigator, Functional neural network analysis in postnatal development of communication ability, Yokoyama Chihiro; Onoe Hirotaka; Hayashi Takuya; Iriki Atsushi; Kato Masaki, Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Institute of Physical and Chemical Research, 13910000, 10700000, 3210000, We investigated brain mechanisms underlying postnatal development of inter-individual communication ability using common marmosets, a primate species known for human-like social activity. The analyses included quantitative evaluation of social behavior and in vivo brain imaging (PET). Early social deprivation results in social withdrawal accompanied with reduced serotonin transporter availability, but late social environment can be expected to restore such effects. Whole-brain mapping of conspecific call perception revealed that the calls convey information about individual identity and context depending on the flexibility of call usage. These results suggested that humans and marmosets may share some neural basis of inter-individual communication. In addition, we report the usefulness of a recently-developed agonist PET probe for 5-HT1A receptor in common marmosets to investigate serotonin system linked with social behavior., Competitive research funding, url
  • 新学術領域研究(研究領域提案型), 01 Apr. 2014, 31 Mar. 2016, 26118517, コモンマーモセットの示す向社会行動の遺伝―環境-脳内神経ネットワーク機能関連, 横山 ちひろ, 日本学術振興会, 科学研究費助成事業 新学術領域研究(研究領域提案型), 国立研究開発法人理化学研究所, 5200000, 4000000, 1200000, 本研究の目的は、向社会行動(利他行動)の生後発達の神経機構を、脳内機能分子および神経ネットワーク機能から明らかにすることである。向社会行動を発現することが知られている非ヒト霊長類であるコモンマーモセットを用いて、以下の項目で実験を実施した。 Ⅰ.向社会行動の定量的評価:利他行動を評価するため、検査者の立ち合いの必要がない自動化されたオペラント行動課題装置の開発を行った。課題ボックスへの移動および馴化を効率化するための改良を重ね、2つの課題ボックスとその間の仕切り版を電磁式可視不可視とする、タッチパネル式TWINケージを導入した。また、自律神経系指標として心血管系動態をモニターするため、小型無線発信機の生体内への装着およびテレメトリー装置によるオンライン測定を行った。 Ⅱ.遺伝子解析:DNAサンプル試料として体毛および頬粘膜を採取し、オピオイド受容体、バソプレシン受容体、ドーパミン受容体の遺伝子多型データを蓄積した。 Ⅱ.脳機能イメージング:養育環境の異なる個体群を用いてセロトニントランスポーター、ドーパミンD2受容体、セロトニン1A受容体特異的PETトレーサーによるPET画像データを蓄積した。マーモセット用MRIコイルの評価、高解像度MRI解剖および機能画像取得に係る動物の麻酔環境、撮像および解析パラメータの最適化を進めた。
  • Grant-in-Aid for Scientific Research (C), 2010, 2012, 22500379, Principal investigator, Neuronal mechanisms for the postnatal development of prosocial behavior, YOKOYAMA Chihiro, Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), The Institute of Physical and Chemical Research, 3900000, 3000000, 900000, We developed the tests for evaluating behavior traits constructing interpersonal relationship in non-human primate species, common marmosets, and examined the brain mechanisms underlying them. The positron emission tomography (PET) for in vivo brain imaging in common marmosets suggested the functional role of serotonin in the midline cortical structures as a part of the social and default mode networks., Competitive research funding, url
  • Grant-in-Aid for Scientific Research (C), 2007, 2009, 19591388, Principal investigator, Molecular basis for sociality associated with gene environmental interaction mechanism, YOKOYAMA Chihiro; MURAYAMA Miho; TAHARA Tsuyoshi; ONOE Hirotaka, Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), The Institute of Physical and Chemical Research, 4420000, 3400000, 1020000, In order to clarify molecular bases for sociality associated with gene-environmental interaction mechanism, we examined the relationship between social behavior and genetic polymorphism or in vivo functional brain imaging revealed by positron emission tomography (PET) in adult common marmosets. We found specific associations for genetic and regional neurochemical aspects with social behavior of individual animals. In addition to that, we revealed the effects of early social deprivation on social behavior associated with these functional molecules., Competitive research funding, url
  • Grant-in-Aid for Scientific Research (B), 2005, 2007, 17390203, Neuropharmacological studies of habitual alcohol drinking behavior in animal models, YOSHIMOTO Kanii; YASUHARA Masahiro, Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B), Kyoto Prefectural University of Medicine, 8480000, 8000000, 480000, Alcohol drinking behavior results from an intricate interplay between genes and environmetal factors, but there remains little understanding of how drinking onset and housing conditions interact to influence on late alcohol drinking behavior. Expression of uncoupling protein-1 (UCP1) in brown adipose tissue (BAT) was studied in young and rats. Mitocondrial UCP1 in BAT is an important key molecule for non-shivering thermogenesis. IP injection of EtOH (2g/kg) caused a decreased expression of BAT UCP1 mRNA in both young and aged rats, but the magnitude of UCP1 mRNA decrease was larger in aged rats than in young rats. Alcohol drinking behavior depends on age of drinking onset and the sensitivity to alcohol associated with functions of ACC DA and 5-HT releases during the process of aging. Mice were injected s.c. with 5, 10 and 20 mg/kg mCPP for 15 days, respectively. Daily intakes of water and 10% ethanol were measured to evaluate alcohol preference (AP) (%) and an alcohol consumption score (g/kg/day).The levels of dopamine (DA) and serotonin (5-H')were analyzed by ECD-HPLC in. the frontal cortex (FC), lateral hypothalamus (LH) and striatum (C/P). MCPP increased AP in a dose-dependently manner. Positive and negative relationships were noted between alcohol consumption score and food intake and mCPP, respectively. MCPP (20mg/kg) increased the level of DA in LH and C/P. The relationship between the levels of 5-HT and mCPP showed a positive correlation in the LH and C/P. The ratios of DOPAC/DA and 5-HIAA/5-HT showed negative correlations with mCPP. It was suggested that the development of alcohol dependence was associated with the down-regulation of 5-HT2c receptor function. Possible underlying reasons for different alcohol drinking behavior in adults include reduced sensitivity to alcohol in the rewarding system and altered responses of the autonomic nerves associated with 5-HT2 receptor functions, e.g., energy dissipation and the stress of housing conditions.
  • Grant-in-Aid for Scientific Research (C), 2005, 2006, 17591226, Principal investigator, Clinical and experimental research on the neural mechanisms underlying developmental disorders, YOKOYAMA Chihiro; FUKUI Kenji; YAMADA Chifuyu; KINOSHITA Seijiro, Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), 京都府立医科大学->独立行政法人理化学研究所, 3500000, 3500000, 0, The aim of the present research is to develop objective tests for the assessment of developmental disorders such as autism and attention deficit hyperactive disorder, which should be relevant to the neural mechanisms underlying them. We studied reversal learning performance as an index for behavioral flexibility in both clinical patients and animal models for developmental disorders. For a clinical use, an automated task for reversal learning was prepared. We made preliminary experiments for measurement of the change in local blood flow in the prefrontal cortex during the task performance by a near-infrared spectroscopy. For experimental studies using animal models, rats with the prefrontal lesions were tested on serial reversal and delayed alternation tasks using odor cues. The prefrontal lesion rats demonstrated selective difficulty in the second reversal in the serial reversal task and impaired variably delayed alternation task. These results suggest that the rat prefrontal cortex mediating monitoring ability in working memory process takes part in reversal learning, which may associated with learning ability of 'reversal' as a concept. Next, we examined rats with serotonin depletion by p-chloroamphetamine in simple and reversal go/no-go visual discrimination tasks. Correlations between serotonin content and learning performance in all animals were assessed in both tests. Serotonin neurotransmission to the prefrontal cortex and amygdala is correlated with inhibitory control ability over responses to discriminated stimuli, while 5-HT neurotransmission to the orbitofrontal cortex is especially involved in additional processes associated with reversal learning. Further studies using animal models and clinical patients are needed to reveal the neural mechanisms underlying specific symptoms of developmental disorders including different types of behavioral flexibility., Competitive research funding, url
  • Grant-in-Aid for Scientific Research (C), 2001, 2002, 13610105, Analysis of the functional anatomy involved in the learning of the visual discrimination task in macaque monkeys., ONOE Hirotaka; YOKOYAMA Chihiro, Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Tokyo Metropolitan Organization for Medical Research, 3300000, 3300000, In monkeys, after the experience of solving hundreds of unique problems of visual discrimination, they become to solve a novel problem very quickly according to the learning-set formation that is defined as learning how to learn the problem. To assess the functional anatomy that is critically involved in learning process of visual discrimination task before and after the learning-set formation, we performed PET study using[^<15>O]-H_2O in monkeys (macaca mulatta). PET images were acquired while monkeys are solving a novel problem of visual discrimination with two geometrical patterns. PET scans were performed at the first experience of the task (an inexperienced novel discrimination, IND), and after the experience of solving several tens of unique problems (an experienced novel discrimination, END). The simple visuomotor task was also conducted as a control. The statistical analysis by SPM revealed that the orbitofrontal, visual, somatosensory, and motor cortices, cerebellum and some subcortical structures were significantly activated in IND, while the dorsolateral prefrontal cortex and visual cortices including higher order areas but not the somatosensory and motor related areas were activated in END. These results indicate that neuronal circuits for the visual discrimination learning dramatically changed depending on their accumulated experience. Recruitments of dorsolateral prefrontal cortex and higher order visual areas could be associated with the learning-set formation for the visual discrimination learning in monkeys.
  • 若手研究(B), 2001, 2002, 13780649, Principal investigator, 高次表象機能獲得の神経科学的基盤-学習機能系の変遷としての学習セット形成-, 横山 ちひろ, 日本学術振興会, 科学研究費助成事業 若手研究(B), (財)大阪バイオサイエンス研究所->京都府立医科大学, 2100000, 2100000, 0, 本研究は、学習セットと名付けられた高次表象機能獲得能を学習機能系の変遷という視点から神経科学的アプローチにより解明するものである。まずアカゲザル(5-7才、6頭)に幾何学図形を用いた同時弁別課題を100新規刺激対からなる新規学習として経験させ、学習期の反応時間を検討した。各新規学習で正解率90%以上の基準に要する試行数は学習経験に依存して有意に減少し、いわゆる「学習セット」の形成が観察された。一方各新規学習で正解率90%以上の基準に満たない時期(学習期)の平均反応時間は学習経験に依存して有意に上昇した。以上の結果は、アカゲザルにおいて視覚弁別学習は学習経験に伴い質的に変化し、学習速度を短縮した学習セット形成後では異なる情報処理過程を用いている可能性を示唆する。次に陽電子断層撮影装置(PET)を用いた脳機能イメージング法により、学習セット形成前後における新規学習に関与する神経回路を調べた。PET装置内で課題遂行中のアカゲザル(4-5才、2頭)で[^<15>O]H_2Oの急速静注法にて脳血流画像を撮像し、経験初回および学習セット課題経験後の新規学習期に、対照運動課題に対し有意な活動を示す領域を画像統計解析により検出した。高次表象機能に関わると予想される前頭前皮質内では、経験初回学習で前頭眼窩皮質が、経験後学習で外側前頭前皮質がそれぞれ特徴的に活動していた。視覚領野は、経験初回学習でも経験後学習でも有意な活動が広く得られたが、経験後学習ではそれに加えて高次視覚連合野である前方下部側頭葉に有意な活動が得られた。体性感覚野、小脳、線条体の有意な活動は、経験初回学習でのみ観察された。以上のように柔軟な学習能力の獲得において、新規学習のための脳ネットワークが多彩な経験によって劇的に変化することが示された。, Competitive research funding, url
  • 奨励研究(A), 1999, 2000, 11770082, Principal investigator, 発達期神経回路形成におよぼす環境化学物質の影響, 横山 ちひろ, 日本学術振興会, 科学研究費助成事業 奨励研究(A), (財)大阪バイオサイエンス研究所, 2100000, 2100000, 0, 本研究における平成11年度の実験の結果から、胎生期の有機溶媒(スチレン)暴露は脳内セロトニン代謝の増加と関連することが示唆された。本年度は脳内アミンと攻撃性との関連を明らかにするため、自然発症的に自傷行為を行う動物での脳内アミン動態について検索した。 実験動物には、音声刺激により自傷行為を呈するニホンザル(5年齢)および対照として同年齢の自傷行為を呈さないニホンザルを用いた。ドーパミンD1受容体拮抗薬SCH23390(0.1mg/kg)およびD2受容体拮抗sulpiride(10mg/kg)の前投薬の効果を調査するため、投薬30分後より音声刺激(15秒毎)と無刺激を各二分間交互に4回行うものを1セッション(一日3セッションX2)としてビデオ撮影し、複数人による観察から自傷行為の持続時間によるスコア化を行った。ドーパミンD1受容体拮抗薬SCH23390(0.1mg/kg)は自傷行為の発現を完全に抑えたがD2受容体拮抗sulpiride(10mg/kg)は部分的効果がしかなかった。続いてPET(陽電子断層撮影装置)を用いて、^<14>C標識したドーパミンD1受容体リガンドとして^<14>C-SCH23390、D2受容体リガンドとして^<14>C-racloprideの結合動態について調べた。その結果自傷行為を呈する動物は対照動物と比べて、前頭前皮質における^<14>C-SCH23390結合能K_1/K_2が高いことがわかった。この結果はアミン神経系、特にドーパミンD1受容体の過感受性が自傷行為発現に関係している行動薬理学的結果と合致しておりその責任部位が前頭前皮質にあることを示唆している。, Competitive research funding, url
  • 奨励研究(A), 1997, 1998, 09780711, Principal investigator, 脳内アミンニューロン系ストレス反応機構におけるサイトカインの関与, 横山 ちひろ, 日本学術振興会, 科学研究費助成事業 奨励研究(A), 川崎医科大学->(財)大阪バイオサイエンス研究所, 2600000, 2600000, 0, 本研究はアミンニューロン系のストレス反応機構について、サイト力インの関与を中心に形態学的手法を用いて明らかにすることを目的とし、具体的には、まずストレス反応神経細胞分布領域を検索するために、成熟ラットに感染ストレスとして0.9%の生理食塩水に溶解したLPS投与(0、25、50、100mg/l00gbodyweight、i.p.)、情動ストレスとして拘束ストレス(30分)を施し、LPS投与60、120、180分後、及び拘束ストレス開始30、60、90分後に潅流固定し、全脳にわたるレベルにおいて抗c-FOS抗体によるABC免疫組織化学を行った。感染ストレスおよび情動ストレスによる視床下部室傍核におけるFOS結合蛋白は、その免疫陽性細胞核の発現数と分布形態においてよく似ていたにもかかわらず、大脳皮質におけるFOS蛋白発現は全く異なる分布を示した(Yokoyama and Sasaki,1999)。また、感染ストレス群および情動ストレス群において、延髄外側被蓋野および青斑核のノルアドレナリンニューロン分布領域にFOS蛋白が発現していたが、前頭前皮質に特異的に投射すると考えられるドーパミンニューロン分布領域である腹側被蓋野正中部では情動ストレス群においてのみFOS蛋白が発現していた(Yokoyama and Sasaki、投稿準備中)。また、LPSおよびサイトカイン投与、または情動ストレス時のアミン代謝回転の脳内各部位での変化について検討の準備段階としてマイクロパンチ法によるアミンとその代謝物の測定のためのHPLC-ECDシステムをたちあげた。, Competitive research funding, url
  • 奨励研究(A), 1995, 1995, 07858085, Principal investigator, 中脳正中部における新しいドーパミン神経細胞群の同定, 横山 ちひろ, 日本学術振興会, 科学研究費助成事業 奨励研究(A), 京都府立医科大学, 900000, 900000, 0, 本研究は、中脳正中部核群-前頭前皮質ドーパミン(DA)神経系の存在とその意義を明らかにすることを目的とし、具体的には以下について検索を行った。 まず、6-hydroxydopamine(6-OHDA)への抵抗性を指標としてその特異的性質を検索した。新生仔期ラットに6-OHDA(100μg/5μl)を大槽内に投与し10週後、抗tyrosine hydroxylase(TH)血清を用いたABC免疫組織化学を施し、中脳において正中より200μm毎に観察されるTH免疫陽性ニューロンをカウントした。その結果、中脳正中部より外側に位置するDAニューロンほど6-OHDA毒性に対する感受性が高いことが明らかになった(Okamuraら、1995)。また、中脳正中部核群DAニューロンがもつNO産生能についての検索を行った。これには抗TH血清と抗NO synthase(NOS)血清を用いた蛍光標識とDAB発色反応を組み合わせた二重標識免疫組織化学を行った。その結果、中脳正中部核群のDAニューロンはNO synthase(NOS)を発現するが、黒質やそれ以外の腹側被蓋野のDAニューロンにはないことを明らかにした(投稿準備中)。 続いて中脳正中部核群DAニューロンの投射系を形態学的に確立するため、トレーサー実験を行った。順行性トレーサーとしてPHA-Lを用いて電気泳動法により中脳腹側部各領域に注入し、抗PHA-L血清を用いた免疫組織化学を行い、それぞれの部位から順行性輸送されたトレーサーを神経終末として観察、その投射領域について現在検索中である。, Competitive research funding, url

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