Research activity information

• Nov. 2022 The Japanese Society of Neuropsychopharmacology, Young Investigator Award, Study on mechanisms and pathophysiological significance of neural circuit formation and plasticity

  Ryota Shinohara


• Jun. 2022 国立大学法人神戸大学, 令和４年度優秀若手研究者賞

  篠原 亮太


• Mar. 2022 The Japanese Pharmacological Society, Young Investigator Award, Elucidation of mechanisms and pathophysiological significance of neural circuit formation and plasticity

  篠原 亮太


• Feb. 2013 Inoue Foundation for Science, 29th Inoue Research Award for Young Scientists

  Ryota Shinohara

  Publisher

• Alteration of COX-1 and TLR4 expression in the mouse brain during chronic social defeat stress revealed by Positron Emission Tomography study.

  Yumika Motooka, Ryota Shinohara, Shiho Kitaoka, Ai Uryu, Dongrui Li, Hiroyuki Neyama, Yilong Cui, Tatsuya Kida, Wakiko Arakaki, Hisashi Doi, Yasuyoshi Watanabe, Tomoyuki Furuyashiki

  Despite the recognized roles of neuroinflammation in mental illnesses, PET imaging on currently available biomarkers has limitations due to the lack of evidence demonstrating their relationship to the molecular and cellular events of inflammation associated with the pathology of mental illness. Rodent stress models, such as chronic social defeat stress (SDS), have identified crucial roles for COX-1 and TLR4, which are innate immune molecules, in chronic SDS-induced neuroinflammation and its behavioral consequences. In this study, we performed COX-1 and TLR4 PET imaging at multiple time points during chronic SDS in mice. For COX-1 PET imaging, we used the COX-1 PET probe (S)-[18F]KTP-Me. Subchronic SDS transiently increased uptake and slower washout in broad regions of the brain, including the cerebral cortex, hippocampus, striatum, and thalamus. For TLR4 PET imaging, we developed a new BBB-permeable PET probe, [11C]1, which detected LPS-induced neuroinflammation. Washout of [11C]1 was facilitated in the cerebellum after subchronic and chronic SDS and in the pons-medulla after chronic SDS. Collectively, our findings suggest the potential usefulness of COX-1 and TLR4 PET imaging in visualizing and understanding time-dependent process of neuroinflammation in stress-related mental illnesses.

  Corresponding, Mar. 2025, Journal of pharmacological sciences, 157(3) (3), 156 - 166, English, Domestic magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• The activation of the piriform cortex to lateral septum pathway during chronic social defeat stress is crucial for the induction of behavioral disturbance in mice

  Yuki Okuda, Dongrui Li, Yuzuki Maruyama, Hirokazu Sonobe, Tomoyuki Mano, Kazuki Tainaka, Ryota Shinohara, Tomoyuki Furuyashiki

  Corresponding, Dec. 2024, Neuropsychopharmacology

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Prefrontal contributions to mental resilience: Lessons from rodent studies of stress and antidepressant actions

  Ryota Shinohara, Tomoyuki Furuyashiki

  Elsevier BV, Dec. 2022, Neuroscience Research, English

  [Refereed][Invited]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Chronic social defeat stress increases the amounts of 12-lipoxygenase lipid metabolites in the nucleus accumbens of stress-resilient mice

  Satoshi Akiyama, Hirotaka Nagai, Shota Oike, Io Horikawa, Masakazu Shinohara, Yabin Lu, Takashi Futamura, Ryota Shinohara, Shiho Kitaoka, Tomoyuki Furuyashiki

  Abstract Severe and prolonged social stress induces mood and cognitive dysfunctions and precipitates major depression. Neuroinflammation has been associated with chronic stress and depression. Rodent studies showed crucial roles of a few inflammation-related lipid mediators for chronic stress-induced depressive-like behaviors. Despite an increasing number of lipid mediators identified, systematic analyses of synthetic pathways of lipid mediators in chronic stress models have not been performed. Using LC–MS/MS, here we examined the effects of chronic social defeat stress on multiple synthetic pathways of lipid mediators in brain regions associated with stress susceptibility in mice. Chronic social defeat stress increased the amounts of 12-lipoxygenase (LOX) metabolites, 12-HETE and 12-HEPE, specifically in the nucleus accumbens 1 week, but not immediately, after the last stress exposure. The increase was larger in stress-resilient mice than stress-susceptible mice. The S isomer of 12-HETE was selectively increased in amount, indicating the role of 12S-LOX activity. Among the enzymes known to have 12S-LOX activity, only Alox12 mRNA was reliably detected in the brain and enriched in brain endothelial cells. These findings suggest that chronic social stress induces a late increase in the amounts of 12S-LOX metabolites derived from the brain vasculature in the nucleus accumbens in a manner associated with stress resilience.

  Springer Science and Business Media LLC, Jul. 2022, Scientific Reports, 12(1) (1), 11385 - 11385, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Neurobiology of the Rapid-Acting Antidepressant Effects of Ketamine: Impact and Opportunities

  Ryota Shinohara, George K. Aghajanian, Chadi G. Abdallah

  Lead, Elsevier BV, Dec. 2020, Biological Psychiatry, English

  [Refereed][Invited]

  Scientific journal


• Cell-type specific modulation of NMDA receptors triggers antidepressant actions

  Santosh Pothula, Taro Kato, Rong-Jian Liu, Min Wu, Danielle Gerhard, Ryota Shinohara, Alexa-Nicole Sliby, Golam M. I. Chowdhury, Kevin L. Behar, Gerard Sanacora, Pradeep Banerjee, Ronald S. Duman

  Springer Science and Business Media LLC, Jun. 2020, Molecular Psychiatry, English

  [Refereed]

  Scientific journal


• Neurobiology of rapid-acting antidepressants: convergent effects on GluA1-synaptic function

  Ronald S. Duman, Ryota Shinohara, Manoela V. Fogaça, Brendan Hare

  Springer Science and Business Media LLC, Dec. 2019, Molecular Psychiatry, 24(12) (12), 1816 - 1832

  [Refereed][Invited]

  Scientific journal


• Social defeat stress-specific increase in c-Fos expression in the extended amygdala in mice: Involvement of dopamine D1 receptor in the medial prefrontal cortex

  Chisato Numa, Hirotaka Nagai, Masayuki Taniguchi, Midori Nagai, Ryota Shinohara, Tomoyuki Furuyashiki

  Springer Science and Business Media LLC, Nov. 2019, Scientific Reports, 9(1) (1)

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Social defeat stress induces phosphorylation of extracellular signal-regulated kinase in the leptomeninges in mice

  Satoshi Okamura, Hirotaka Nagai, Chisato Numa, Midori Nagai, Ryota Shinohara, Tomoyuki Furuyashiki

  Wiley, Jun. 2019, Neuropsychopharmacology Reports, 39(2) (2), 134 - 139

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects

  Brendan D. Hare, Ryota Shinohara, Rong Jian Liu, Santosh Pothula, Ralph J. DiLeone, Ronald S. Duman

  Springer Science and Business Media LLC, Jan. 2019, Nature Communications, 10(1) (1)

  [Refereed]

  Scientific journal


• Repeated social defeat stress impairs attentional set shifting irrespective of social avoidance and increases female preference associated with heightened anxiety

  Shu Higashida, Hirotaka Nagai, Kazuki Nakayama, Ryota Shinohara, Masayuki Taniguchi, Midori Nagai, Takatoshi Hikida, Satoshi Yawata, Yukio Ago, Shiho Kitaoka, Shuh Narumiya, Tomoyuki Furuyashiki

  Lead, Springer Science and Business Media LLC, Dec. 2018, Scientific Reports, 8(1) (1)

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Dopamine D1 receptor subtype mediates acute stress-induced dendritic growth in excitatory neurons of the medial prefrontal cortex and contributes to suppression of stress susceptibility in mice

  R Shinohara, M Taniguchi, A T Ehrlich, K Yokogawa, Y Deguchi, Y Cherasse, M Lazarus, Y Urade, A Ogawa, S Kitaoka, A Sawa, S Narumiya, T Furuyashiki

  Lead, Springer Science and Business Media LLC, Aug. 2018, Molecular Psychiatry, 23(8) (8), 1717 - 1730

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Characterization of a novel rhamnose-containing acidic glycosphingolipid from the ascidian Halocynthia aurantium

  Hisao Kojima, Ryota Shinohara, Saki Itonori, Masahiro Ito

  Halocynthia aurantium, an edible ascidian species belonging to Urochordata, was subjected to structural characterization of acidic glycosphingolipids to investigate these molecules in ascidians: sulfatide from Ciona intestinalis and the glucuronic acid-containing acidic glycosphingolipid from H. roretzi. Acidic glycosphingolipids containing three or five sugars were isolated from soft parts of the ascidian H. aurantium by chloroform-methanol extraction, mild-alkaline hydrolysis, precipitation with cold acetone, and subsequent column chromatography using a DEAE-Sephadex A-25 column, a Florisil column, and an Iatrobead column. The structures of these glycosphingolipids were determined by methylation studies, sugar analysis, fatty acid analysis, sphingoid analysis, mass spectrometry, and proton nuclear magnetic resonance spectroscopy. A novel glucuronic acid-containing glycosphingolipid having a rhamnose residue was identified as Rhaα1-3GlcNAcβ1-3Galβ1-4(Fucα1-3)GlcAβ1-Cer (UGL-2). This novel structure is particularly unusual given that it contains both a rhamnose residue and a reducing terminal glucuronic acid residue within a single molecule. Rhamnose is a characteristic sugar, which is a component of cell wall pectin in plants and exopolysaccharides in bacteria. Ascidians acquired the cellulose synthase gene via lateral gene transfer, and therefore, it can be speculated that they also acquired the rhamnosyltransferase gene in the same manner. We also detected Galβ1-4(Fucα1-3)GlcAβ1-Cer (UGL-1), which was already identified in another ascidian, H. roretzi.

  Lead, Japan Oil Chemists Society, 2017, Journal of Oleo Science, 66(3) (3), 285 - 295, English

  [Refereed]

  Scientific journal


• mDia and ROCK Mediate Actin-Dependent Presynaptic Remodeling Regulating Synaptic Efficacy and Anxiety

  Yuichi Deguchi, Masaya Harada, Ryota Shinohara, Michael Lazarus, Yoan Cherasse, Yoshihiro Urade, Daisuke Yamada, Masayuki Sekiguchi, Dai Watanabe, Tomoyuki Furuyashiki, Shuh Narumiya

  Here, we show neuronal inactivation-induced presynaptic remodeling and involvement of the mammalian homolog of Diaphanous (mDia) and Rho-associated coiled-coil-containing kinase (ROCK), Rho-regulated modulators of actin and myosin, in this process. We find that social isolation induces inactivation of nucleus accumbens (NAc) neurons associated with elevated anxiety-like behavior, and that mDia in NAc neurons is essential in this process. Upon inactivation of cultured neurons, mDia induces circumferential actin filaments around the edge of the synaptic cleft, which contract the presynaptic terminals in a ROCK-dependent manner. Social isolation induces similar mDia-dependent presynaptic contraction at GABAergic synapses from NAc neurons in the ventral tegmental area (VTA) associated with reduced synaptic efficacy. Optogenetic stimulation of NAc neurons rescues the anxiety phenotype, and injection of a specific ROCK inhibitor, Y-27632, into the VTA reverses both presynaptic contraction and the behavioral phenotype. mDia-ROCK signaling thus mediates actin-dependent presynaptic remodeling in inactivated NAc neurons, which underlies synaptic plasticity in emotional behavioral responses.

  Elsevier B.V., Nov. 2016, Cell Reports, 17(9) (9), 2405 - 2417, English

  [Refereed]

  Scientific journal


• The combined effect of clothianidin and environmental stress on the behavioral and reproductive function in male mice

  Tetsushi Hirano, Shogo Yanai, Takuya Omotehara, Rie Hashimoto, Yuria Umemura, Naoto Kubota, Kiichi Minami, Daichi Nagahara, Eiko Matsuo, Yoshiko Aihara, Ryota Shinohara, Tomoyuki Furuyashiki, Youhei Mantani, Toshifumi Yokoyama, Hiroshi Kitagawa, Nobuhiko Hoshi

  Neonicotinoids, some of the most widely used pesticides in the world, act as agonists to the nicotinic acetylcholine receptors (nAChRs) of insects, resulting in death from abnormal excitability. Neonicotinoids unexpectedly became a major topic as a compelling cause of honeybee colony collapse disorder, which is damaging crop production that requires pollination worldwide. Mammal nAChRs appear to have a certain affinity for neonicotinoids with lower levels than those of insects there is thus rising concern about unpredictable adverse effects of neonicotinoids on vertebrates. We hypothesized that the effects of neonicotinoids would be enhanced under a chronic stressed condition, which is known to alter the expression of targets of neonicotinoids, i.e., neuronal nAChRs. We performed immunohistochemical and behavioral analyses in male mice actively administered a neonicotinoid, clothianidin (CTD 0, 10, 50 and 250 mg/kg/day), for 4 weeks under an unpredictable chronic stress procedure. Vacuolated seminiferous epithelia and a decrease in the immunoreactivity of the antioxidant enzyme glutathione peroxidase 4 were observed in the testes of the CTD+stress mice. In an open field test, although the locomotor activities were not affected, the anxiety-like behaviors of the mice were elevated by both CTD and stress. The present study demonstrates that the behavioral and reproductive effects of CTD become more serious in combination with environmental stress, which may reflect our actual situation of multiple exposure.

  Japanese Society of Veterinary Science, Nov. 2015, Journal of Veterinary Medical Science, 77(10) (10), 1207 - 1215, English

  [Refereed]

  Scientific journal


• EphA4-dependent axon retraction and midline localization of Ephrin-B3 are disrupted in the spinal cord of mice lacking mDia1 and mDia3 in combination.

  Yosuke Toyoda, Ryota Shinohara, Dean Thumkeo, Hiroshi Kamijo, Hiroshi Nishimaru, Hiroyuki Hioki, Takeshi Kaneko, Toshimasa Ishizaki, Tomoyuki Furuyashiki, Shuh Narumiya

  mDia is an actin nucleator and polymerization factor regulated by the small GTPase Rho and consists of three isoforms. Here, we found that mice lacking mDia1 and mDia3, two isoforms expressed in the brain, in combination (mDia-DKO mice) show impaired left-right limb coordination during locomotion and aberrant midline crossing of axons of corticospinal neurons and spinal cord interneurons. Given that mice lacking Ephrin-B3-EphA4 signaling show a similar impairment in locomotion, we examined whether mDia is involved in Ephrin-B3-EphA4 signaling for axon repulsion. In primary cultured neurons, mDia deficiency impairs growth cone collapse and axon retraction induced by chemo-repellants including EphA ligands. In mDia-DKO mice, the Ephrin-B3-expressing midline structure in the spinal cord is disrupted, and axons aberrantly cross the spinal cord midline preferentially through the region devoid of Ephrin-B3. Therefore, mDia plays multiple roles in the proper formation of the neural network in vivo.

  Lead, Wiley, Oct. 2013, Genes to cells : devoted to molecular & cellular mechanisms, 18(10) (10), 873 - 85, English, International magazine

  [Refereed]

  Scientific journal


• A role for mDia, a Rho-regulated actin nucleator, in tangential migration of interneuron precursors

  Ryota Shinohara, Dean Thumkeo, Hiroshi Kamijo, Naoko Kaneko, Kazunobu Sawamoto, Keisuke Watanabe, Hirohide Takebayashi, Hiroshi Kiyonari, Toshimasa Ishizaki, Tomoyuki Furuyashiki, Shuh Narumiya

  In brain development, distinct types of migration, radial migration and tangential migration, are shown by excitatory and inhibitory neurons, respectively. Whether these two types of migration operate by similar cellular mechanisms remains unclear. We examined neuronal migration in mice deficient in mDia1 (also known as Diap1) and mDia3 (also known as Diap2), which encode the Rho-regulated actin nucleators mammalian diaphanous homolog 1 (mDia1) and mDia3. mDia deficiency impaired tangential migration of cortical and olfactory inhibitory interneurons, whereas radial migration and consequent layer formation of cortical excitatory neurons were unaffected. mDia-deficient neuroblasts exhibited reduced separation of the centrosome from the nucleus and retarded nuclear translocation. Concomitantly, anterograde F-actin movement and F-actin condensation at the rear, which occur during centrosomal and nuclear movement of wild-type cells, respectively, were impaired in mDia-deficient neuroblasts. Blockade of Rho-associated protein kinase (ROCK), which regulates myosin II, also impaired nuclear translocation. These results suggest that Rho signaling via mDia and ROCK critically regulates nuclear translocation through F-actin dynamics in tangential migration, whereas this mechanism is dispensable in radial migration. © 2012 Nature America, Inc. All rights reserved.

  Lead, Springer Science and Business Media LLC, Mar. 2012, Nature Neuroscience, 15(3) (3), 373 - 380, English

  [Refereed]

  Scientific journal


• Deficiency of mDia, an actin nucleator, disrupts integrity of neuroepithelium and causes periventricular dysplasia

  Dean Thumkeo, Ryota Shinohara, Keisuke Watanabe, Hirohide Takebayashi, Yosuke Toyoda, Kiyoshi Tohyama, Toshimasa Ishizaki, Tomoyuki Furuyashiki, Shuh Narumiya

  During development of the central nervous system, the apical-basal polarity of neuroepithelial cells is critical for homeostasis of proliferation and differentiation of neural stem cells. While adherens junctions at the apical surface of neuroepithelial cells are important for maintaining the polarity, the molecular mechanism regulating integrity of these adherens junctions remains largely unknown. Given the importance of actin cytoskeleton in adherens junctions, we have analyzed the role of mDia, an actin nucleator and a Rho effector, in the integrity of the apical adherens junction. Here we show that mDia1 and mDia3 are expressed in the developing brain, and that mDia3 is concentrated in the apical surface of neuroepithelium. Mice deficient in both mDia1 and mDia3 develop periventricular dysplastic mass widespread throughout the developing brain, where neuroepithelial cell polarity is impaired with attenuated apical actin belts and loss of apical adherens junctions. In addition, electron microscopic analysis revealed abnormal shrinkage and apical membrane bulging of neuroepithelial cells in the remaining areas. Furthermore, perturbation of Rho, but not that of ROCK, causes loss of the apical actin belt and adherens junctions similarly to mDia-deficient mice. These results suggest that actin cytoskeleton regulated by Rho-mDia pathway is critical for the integrity of the adherens junctions and the polarity of neuroepithelial cells, and that loss of this signaling induces aberrant, ectopic proliferation and differentiation of neural stem cells. © 2011 Thumkeo et al.

  Lead, Public Library of Science (PLoS), Sep. 2011, PLoS ONE, 6(9) (9), e25465 - e25465, English

  [Refereed]

  Scientific journal


• Sphingomyelins in four ascidians, Ciona intestinalis, Halocynthia roretzi, Halocynthia aurantium, and Styela clava

  Masahiro Ito, Kazuhito Yokoi, Takashi Inoue, Shogo Asano, Rei Hatano, Ryota Shinohara, Saki Itonori, Mutsumi Sugita

  Sphingomyelin is rarely found in lower animals, while sphingophospholipid is a characteristic of higher animals. In this study, sphingomyelin was first isolated and characterized from ascidian Ciona intestinalis. Ascidian sphingomyelin was prepared using ion exchange (QAE-Sphadex-A25) and silicic acid (Florisil and Iatrobeads) column chromatographies. The chemical structure was characterized by fatty acid analysis, sphingoid analysis, hydrogen fluoride degradation, acid hydrolysis, enzymatic hydrolysis, infrared analysis, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The ceramide moieties of C. intestinalis sphingomyelin consisted primarily of C16:0, C18:0, and C18:1 fatty acids and d18:2 sphingadiene. Furthermore, sphingomyelins were isolated and characterized from 3 other ascidians, Halocynthia roretzi, Halocynthia aurantium, and Styela clava using the same methods. Comparative analysis of the sphingomyelin structures in 4 ascidian species-C. intestinalis (Enterogona) and H. roretzi, H. aurantium, and S. clava (Pleurogona)-revealed that the major fatty acid composition of the ceramides was similar, and that they differed in minor components. © 2009 by Japan Oil Chemists' Society.

  Japan Oil Chemists Society, Aug. 2009, Journal of Oleo Science, 58(9) (9), 473 - 480, English

  [Refereed]

  Scientific journal

• レジリエンスにおける前頭前皮質ドパミン系の役割

  Ryota Shinohara

  Lead, Mar. 2023, Medical Science Digest, 49(3) (3)

  [Invited]


• Chronic social stress causes long-term structural alterations of neuronal projections to the medial prefrontal cortex in mice

  Yuki Okuda, Ryota Shinohara, Hirokazu Sonobe, Yuzuki Maruyama, Masahiro Yamaguchi, Kei Ito, Akinori Sato, Fumitaka Osakada, Tomoyuki Furuyashiki

  Japanese Pharmacological Society, 2023, Proceedings for Annual Meeting of The Japanese Pharmacological Society, 97, 2 - B


• Neutrophil mobilization is crucial for chronic social stress-induced behavioral alterations in mice

  Toshihiro Hisasue, Qing Zhu, Yuka Ishikawa, Taro Kato, Shinichi Ishii, Yoshio Katayama, Yuta Yamaguchi, Ryota Shinohara, Tomoyuki Furuyashiki

  Japanese Pharmacological Society, 2023, Proceedings for Annual Meeting of The Japanese Pharmacological Society, 97, 3 - B


• Neural circuit mechanisms of rapid antidepressant actions of ketamine

  Ryota Shinohara

  Lead, Japanese Pharmacological Society, Sep. 2022, Folia Pharmacologica Japonica, 157(5) (5), 386 - 386

  [Refereed][Invited]


• Distinct downstream targets of the medial prefrontal cortex underlie discrete antidepressant responses to ketamine

  Ryota Shinohara, Brendan D. Hare, Rong-Jian Liu, Jin Hua Li, Xiao-Yuan Li, Catharine H. Duman, Ralph J. DiLeone, Ronald S. Duman

  Japanese Pharmacological Society, 2022, Proceedings for Annual Meeting of The Japanese Pharmacological Society, 95, 1 - O


• Elucidation of mechanisms and pathophysiological significance of neural circuit formation and plasticity

  Ryota Shinohara

  Japanese Pharmacological Society, 2022, Proceedings for Annual Meeting of The Japanese Pharmacological Society, 95, 3 - YAL3


• Analysis of neural circuit alterations caused by chronic social stress

  Ryota Shinohara, Yuki Okuda, Masahiro Yamaguchi, Fumitaka Osakasa, Tomoyuki Furuyashiki

  Japanese Pharmacological Society, 2022, Proceedings for Annual Meeting of The Japanese Pharmacological Society, 96, 3 - B


• 内側前頭前皮質と扁桃体の分子変化からみたストレス・レジリエンス

  Ryota Shinohara

  Lead, 2021, CLINICAL NEUROSCIENCE, 39(6) (6)

  [Invited]


• Roles of the dopaminergic system in the medial prefrontal cortex for stress resilience and its relevance to stress-induced changes in neuronal morphology

  TANIGUCHI, Masayuki, SHINOHARA, Ryota, FURUYASHIKI, Tomoyuki

  2018, Japanese Journal of Biological Psychiatry, 29(1) (1), 27 - 33, Japanese

  [Refereed][Invited]

  Introduction scientific journal


• Neural circuits regulating stress resilience

  SHINOHARA, Ryota

  Lead, The Japanese Pharmacological Society, Nov. 2017, Nihon Yakurigaku Zasshi, 150(5) (5), 261 - 261, Japanese

  [Refereed][Invited]

  Introduction scientific journal


• アルコール・薬物依存症の細胞薬理学 ドパミン神経変容の展望 内側前頭前皮質のドパミン受容体サブタイプによるストレス抵抗性増強と神経回路リモデリング

  SHINOHARA Ryota

  Aug. 2016, 日本アルコール・薬物医学会雑誌, 51(4号) (4号), 105, Japanese

  [Invited]


• 情動行動制御への前頭前皮質の関与とその異常 前頭前皮質ドパミン系によるストレスレジリエンスの増強

  SHINOHARA Ryota, 谷口将之, エーリック・アリザ, 横川賢多朗, 出口雄一, 小川淳史, 北岡志保, 澤明, 成宮周, 古屋敷智之

  Jul. 2016, 日本神経精神薬理学会年会プログラム・抄録集 46回, 92, Japanese

  [Invited]


• Dopamine D1 receptor in the medial prefrontal cortex mediates behavioral resilience under stress in mice

  Ryota Shinohara, Yuichi Deguchi, Aliza Ehrlich, Tomoyuki Furuyashiki, Shiho Kitaoka, Shuh Narumiya, Atsubumi Ogawa, Akira Sawa, Masayuki Taniguchi, Kentarou Yokogawa

  OXFORD UNIV PRESS, Jun. 2016, INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY, 19, 96 - 96, English

  Summary international conference


• Roles of dopaminergic and inflammation-related molecular derived from microglia in stress-induced behavioral changes

  SHINOHARA Ryota, KITAOKA Shiho, FURUYASHIKI Tomoyuki

  Repeated stress induces emotional changes and cognitive impairments, and is a risk factor for psychiatric disorders. Rodent studies have revealed critical roles of dopaminergic systems and inflammation-related molecules derived from microglia in repeated stress-induced behavioral changes. Acute stress preferentially activates the dopaminergic pathway projecting to the medial prefrontal cortex (mPFC) through glucocorticoid receptor. This dopaminergic activation impairs working memory functions, but suppresses stress-induced social avoidance. Repeated stress attenuates this dopaminergic pathway, and consequently impairs working memory function and promotes stress-induced social avoidance. In contrast, repeated stress increases the excitability of the dopaminergic pathway projecting to the nucleus accumbens (NAc), from which BDNF is released in NAc and promotes stress-induced social avoidance and anhedonia. In addition, repeated stress induces expression of inflammation-related molecules in microglia through beta-adrenergic receptors. Under repeated stress, IL-1 beta induces behavioral depression and anxiety, perhaps partly through suppressing proliferation of neural stem cells in the hippocampus. IL-1 receptor signaling in endothelial cells augments expression of inflammation-related cytokines in microglia, thereby promoting stress-induced behavioral changes. TNF alpha and IL-6 are also critical for stress-induced depression-like behaviors. Repeated stress increases synthesis of prostaglandin (PG) E2 in microglia through PG synthase COX1. PGE2 in turn attenuates the dopaminergic pathway to mPFC through EP1 receptor, thereby promoting social avoidance by repeated stress. These findings show that repeated stress induces behavioral changes through neurotransmitters and inflammation-related molecules as well as the crosstalk between neurons and microglia.

  Lead, JAPANESE ASSOC STUDY PAIN, Mar. 2016, PAIN RESEARCH, 31(1号) (1号), 1 - 8, Japanese

  [Refereed][Invited]

  Introduction scientific journal


• ROCK

  篠原 亮太, 出口 雄一, 古屋敷 智之

  Lead, 2016, 脳科学辞典

  [Refereed][Invited]


• A role for mDia, a Rho-regulated actin nucleator, in regulating morphology of presynaptic terminals and increased anxiety-like behavior induced by social isolation stress in mice

  Yuichi Deguchi, Masaya Harada, Ryota Shinohara, Michael Lazarus, Yoan Cherasse, Yoshihiro Urade, Dai Watanabe, Tomoyuki Furuyashiki, Shuh Narumiya

  JAPANESE PHARMACOLOGICAL SOC, Jul. 2015, JOURNAL OF PHARMACOLOGICAL SCIENCES, 128(3) (3), S92 - S92, English

  Summary international conference


• A role for dopamine D1 receptor in the medial prefrontal cortex in stress-induced emotional changes

  Ryota Shinohara, Masayuki Taniguchi, Aliza Ehrlich, Kentaro Yokogawa, Shuh Narumiya, Tomoyuki Furuyashiki

  JAPANESE PHARMACOLOGICAL SOC, Jul. 2015, JOURNAL OF PHARMACOLOGICAL SCIENCES, 128(3) (3), S227 - S227, English

  Summary international conference


• Roles of mDia1/3 in neuroepithelium integrity and neuroblast migration

  D. Thumkeo, R. Shinohara, S. Narumiya

  AMER SOC CELL BIOLOGY, 2015, MOLECULAR BIOLOGY OF THE CELL, 26, English

  Summary international conference


• A role for mDia, a Rho-regulated actin nucleator, in elevated anxiety induced by social isolation stress in mice

  Yuichi Deguchi, Masaya Harada, Ryota Shinohara, Michael Lazarus, Yoan Cherasse, Yoshihiro Urade, Tomoyuki Furuyashiki, Shuh Narumiya

  JAPANESE PHARMACOLOGICAL SOC, 2014, JOURNAL OF PHARMACOLOGICAL SCIENCES, 124, 98P - 98P, English

  Summary international conference


• Functional changes of the medial prefrontal cortex induced by repeated social defeat stress in mice

  Ryota Shinohara, Aliza Ehrlich, Kentaro Yokogawa, Shuh Narumiya, Tomoyuki Furuyashiki

  JAPANESE PHARMACOLOGICAL SOC, 2014, JOURNAL OF PHARMACOLOGICAL SCIENCES, 124, 217P - 217P, English

  Summary international conference


• 輝け次代の担い手たち 神経発生におけるRho標的アクチン重合因子mDiaの役割

  SHINOHARA Ryota

  Lead, Mar. 2013, 神経化学, 52(1号) (1号), 13 - 21, Japanese

  [Invited]

  Introduction scientific journal


• アクチン

  篠原 亮太, 古屋敷 智之

  Lead, 2013, 脳科学辞典

  [Refereed][Invited]


• Roles of mDia, a Rho effector and formin family actin-nucleator, in T cell development

  Dean Thumkeo, Akira Nomachi, Kiyoshi Tohyama, Ryota Shinohara, Takako Hirata, Toshimasa Ishizaki, Shuh Narumiya

  JAPANESE PHARMACOLOGICAL SOC, 2013, JOURNAL OF PHARMACOLOGICAL SCIENCES, 121, 63P - 63P, English

  [Refereed]

  Summary international conference


• Rhoファミリー低分子量Gタンパク質

  篠原 亮太, 古屋敷 智之

  Lead, 2012, 脳科学辞典

  [Refereed][Invited]


• mDia, a Rho effector and actin nucleator, is critical for growth cone retraction in ephrin-induced axonal repulsion

  豊田 洋輔, 篠原 亮太, タムケオ・ディーン, 上條 博史, 日置 寛之, 金子 武嗣, 石崎 敏理, 古屋敷 智之, 成宮 周

  (公社)日本生化学会, Sep. 2011, 日本生化学会大会プログラム・講演要旨集, 84回, 3P - 0588, Japanese


• Rho signaling in developing nervous system

  Dean Thumkeo, Ryota Shinohara, Shuh Narumiya

  JAPANESE PHARMACOLOGICAL SOC, 2011, JOURNAL OF PHARMACOLOGICAL SCIENCES, 115, 29P - 29P, English

  Summary international conference


• Roles of mDia isoforms, a Rho effector, in neuroblast migration

  Shinohara Ryota, Thumkeo Dean, Kamijo Hiroshi, Kaneko Naoko, Sawamoto Kazunobu, Watanabe Keisuke, Takebayashi Hirohide, Ishizaki Toshimasa, Furuyashiki Tomoyuki, Narumiya Shuh

  2011, JOURNAL OF PHARMACOLOGICAL SCIENCES, 115, 133P

  [Refereed]


• mDia, an actin nucleator and a Rho effector, is critical for tangential migration of cortical and olfactory bulb inhibitory interneuron precursors

  Shinohara Ryota, Thumkeo Dean, Kamijo Hiroshi, Kaneko Naoko, Sawamoto Kazunobu, Watanabe Keisuke, Takebayashi Hirohide, Kiyonari Hiroshi, Ishizaki Toshimasa, Furuyashiki Tomoyuki, Narumiya Shuh

  (公社)日本生化学会, 2011, NEUROSCIENCE RESEARCH, 71, E130 - 0587, Japanese

  [Refereed]


• Roles of mDia isoforms, a Rho effector, in neural development

  Ryota Shinohara, Dean Thumkeo, Hiroshi Kamijo, Naoko Kaneko, Kazunobu Sawamoto, Hiroyuki Hioki, Takeshi Kaneko, Keisuke Watanabe, Hirohide Takebayashi, Toshimasa Ishizaki, Tomoyuki Furuyashiki, Shuh Narumiya

  Elsevier BV, Jan. 2010, Neuroscience Research, 68, e138 - e138


• Roles of mDia, a Rho effector, in neural development

  Ryota Shinohara, Hiroshi Kamijo, Hiroyuki Hioki, Takeshi Kaneko, Toshimasa Ishizaki, Tomoyuki Furuyashiki, Shuh Narumiya

  Elsevier BV, Jan. 2009, Neuroscience Research, 65, S95 - S95

• The prefrontal dopaminergic system underlies stress resilience and antidepressant effects of ketamine

  Ryota Shinohara

  APPW2025, Mar. 2025, English

  Public symposium


• 慢性ストレスによる神経回路再編と行動変容での役割

  篠原亮太

  2024年度生理学研究所研究会「情動研究会2024」, Sep. 2024

  [Invited]

  Nominated symposium


• Alterations in prefrontal cortex circuits caused by chronic social stress

  Ryota Shinohara, Yuki Okuda, Hirokazu Sonobe, Masahiro Yamaguchi, Kei N. Ito, Akinori Sato, Fumitaka Osakada, Tomoyuki Furuyashiki

  The 46th Annual Meeting of the Japan Neuroscience Society, Aug. 2023


• Roles of prefrontal dopamine D1 receptors in stress resilience and antidepressant actions of ketamine

  Ryota Shinohara

  「次世代脳」プロジェクト 冬のシンポジウム2022 新学術領域「マルチスケール脳」企画シンポジウム, Dec. 2022, English

  [Invited]

  Nominated symposium


• Analysis of neural circuit alterations caused by chronic social stress

  Ryota Shinohara, Yuki Okuda, Masahiro Yamaguchi, Fumitaka Osakada, Tomoyuki Furuyashiki

  The 96th Annual Meeting of the Japanese Pharmacological Society, Dec. 2022, Japanese

  Oral presentation


• Study on mechanisms and pathophysiological significance of neural circuit formation and plasticity

  Ryota Shinohara

  BPCNPNPPP2022 (Japanese Society of Neuropsychopharmacology Young Investigator Award Lecture), Nov. 2022, Japanese

  [Invited]

  Invited oral presentation


• Elucidation of mechanisms and pathophysiological significance of neural circuit formation and plasticity

  Ryota Shinohara

  The 95th Annual Meeting of the Japanese Pharmacological Society (The 37th Encouragement of Young Investigator Award Lecture), Mar. 2022, Japanese

  [Invited]

  Invited oral presentation


• Distinct downstream targets of the medial prefrontal cortex underlie discrete antidepressant responses to ketamine

  Ryota Shinohara, Brendan D. Hare, Rong-Jian Liu, Jin Hua Li, Xiao-Yuan Li, Catharine H. Duman, Ralph J. DiLeone, Ronald, S. Duman

  The 95th Annual Meeting of the Japanese Pharmacological Society, Mar. 2022, Japanese

  Oral presentation


• Distinct downstream targets of the medial prefrontal cortex underlie discrete antidepressant responses to ketamine

  Ryota Shinohara, Brendan D. Hare, Rong-Jian Liu, Jin Hua Li, Xiao-Yuan Li, Catharine H. Duman, Ralph J. DiLeone, Ronald, S. Duman

  14th Asia Pacific Federation of Pharmacologists (APFP2021), Nov. 2021, English

  [Invited]

  Invited oral presentation


• A neural circuit mechanism underlying rapid antidepressant actions of ketamine

  Ryota Shinohara

  京都大学大学院医学研究科 創薬医学講座セミナー, Nov. 2021, Japanese

  [Invited]

  Invited oral presentation


• ケタミンの即効性抗うつ作用を担う神経回路基盤

  篠原 亮太

  2021年度生理学研究所研究会「情動研究会2021」, Sep. 2021, Japanese

  [Invited]

  Invited oral presentation


• A neural circuit mechanism underlying rapid antidepressant actions of ketamine

  Ryota Shinohara, Brendan D Hare, Rong-Jian Liu, Jin Hua Li, Xiao-Yuan Li, Catharine H Duman, Ralph J DiLeone, Ronald S Duman

  The 44th Annual Meeting of the Japan Neuroscience Society / The 1st CJK International Meeting, Jul. 2021, English

  Oral presentation


• Distinct projection targets of dopamine D1 receptor-expressing neurons in the prefrontal cortex underlying antidepressant responses to ketamine

  Ryota Shinohara, Brendan D. Hare, Rong-Jian Liu, Jin Hua, Li, Xiao-Yuan Li, Catharine H. Duman, Ralph J. DiLeone, Ronald S. Duman

  The 43rd Annual Meeting of the Japanese Society of Biological Psychiatry (JSBP) / The 51st Annual Meeting of the Japanese Society of Neuropsychopharmacology (JSNP), Jul. 2021

  Oral presentation


• Roles of the prefrontal dopaminergic system in stress resilience and rapid antidepressant responses

  Ryota Shinohara

  IBS Center for Cognition and Sociality Seminar, Mar. 2021, English

  [Invited]

  Invited oral presentation


• Distinct projections of the medial prefrontal cortex underlie the rapid antidepressant actions of ketamine

  Shinohara, R., Hare, B.D., Liu, R.J., Duman, R.S.

  Neuroscience 2019, Oct. 2019, English, Society for Neuroscience, Chicago, IL, United States, International conference

  Poster presentation


• Dissecting neural circuits underlying stress and rapid antidepressant actions in animal models

  Ryota Shinohara

  Biological Sciences Training Program (BSTP) Seminar Series, Sep. 2019, English, Department of Psychiatry, Yale University School of Medicine, United States

  [Invited]

  Public discourse


• Identifying the molecular and neural circuit mechanisms of the action of rapid-acting antidepressants

  SHINOHARA, Ryota

  The 42nd Annual Meeting of the Japan Neuroscience Society, Jul. 2019, English, Domestic conference

  [Invited]

  Nominated symposium


• Projection-specific optogenetic stimulation of medial prefrontal cortex neurons expressing dopamine D1 receptors produces rapid antidepressant effects

  Shinohara, R., Hare, B.D., Pothula, S., Duman, R.S.

  Neuroscience 2018, Nov. 2018, English, Society for Neuroscience, San Diego, CA, United States, International conference

  Poster presentation


• Dopamine D1 receptor mediates social defeat stress-induced dendritic growth in excitatory neurons of the medial prefrontal cortex and suppresses stress susceptibility in mice

  Ryota Shinohara, Masayuki Taniguchi, Aliza T. Ehrlich, Kentarou Yokogawa, Yuichi Deguchi, Atsubumi Ogawa, Shiho Kitaoka, Akira Sawa, Shuh Narumiya, Tomoyuki Furuyashiki

  The 40th Annual Meeting of the Japan Neuroscience Society, Jul. 2017, English, Domestic conference

  Oral presentation


• Dopamine D1 receptor in excitatory neurons in the medial prefrontal cortex suppresses emotional changes induced by social defeat stress

  Shinohara Ryota, 谷口 将之, 成宮 周, Furuyashiki Tomoyuki

  The 130th Kinki Regional Meeting of the Japanese Pharmacological Society, Nov. 2016, Japanese, 日本薬理学会, 京都, Domestic conference

  Oral presentation


• 内側前頭前皮質のドパミン受容体サブタイプによるストレス抵抗性増強と神経回路リモデリング

  Shinohara Ryota, 谷口 将之, Furuyashiki Tomoyuki

  51st Japanese Medical Society of Alcohol and Addiction Studies, Oct. 2016, Japanese, 日本アルコール・アディクション医学会, 東京, Domestic conference

  [Invited]

  Nominated symposium


• A role for prefrontal dopaminergic system in regulating stress resilience

  Shinohara Ryota, 谷口 将之, エーリック アリザ, 横川 賢多朗, 出口 雄一, 小川 淳史, Kitaoka Shiho, 澤 明, 成宮 周, Furuyashiki Tomoyuki

  46th Annual Meeting of the Japanese Society of Neuropsychopharmacology, Jul. 2016, Japanese, 日本神経精神薬理学会, ソウル, 韓国, Domestic conference

  [Invited]

  Invited oral presentation


• Dopamine D1 receptor in the medial prefrontal cortex mediates behavioral resilience under stress in mice

  Shinohara Ryota, 谷口 将之, エーリック アリザ, 横川 賢多朗, 出口 雄一, 小川 淳史, Kitaoka Shiho, 澤 明, 成宮 周, Furuyashiki Tomoyuki

  CINP 2016 Seoul World Congress (Seoul), Jul. 2016, English, The International College of Neuropsychopharmacology (CINP), ソウル, 韓国, International conference

  Poster presentation


• Dopamine D1 receptor in the medial prefrontal cortex regulates susceptibility to social defeat stress

  Ryota Shinohara, Masayuki Taniguchi, Aliza T. Rhrlich, Kentarou Yokogawa, Akira Sawa, Shuh Narumiya, Tomoyuki Furuyashiki

  The 38th Annual Meeting of the Japan Neuroscience Society, Jul. 2015, English, Kobe, Japan, Domestic conference

  Oral presentation


• A role for dopamine D1 receptor in the medial prefrontal cortex in stress-induced emotional changes

  SHINOHARA, Ryota

  Ritsumeikan University 6th Symposium of Next Generation Drug Discovery, Mar. 2015, Japanese

  [Invited]

  Nominated symposium


• mDia, a Rho-regulated actin nucleator, is critical for tangential migration of inhibitory interneuron precursors

  SHINOHARA, Ryota

  Kyoto University Global COE Program “Center for Frontier Medicine” International Symposium 2012, Oct. 2012, English

  [Invited]

  Nominated symposium


• mDia, an actin nucleator and a Rho effector, is critical for tangential migration of cortical and olfactory bulb inhibitory interneuron precursors

  Shinohara, R., Thumkeo, D., Kamijo, H, Kaneko, N., Sawamoto, K., Watanabe, K., Takebayashi, H., Ishizaki, T, Furuyashiki, T., Narumiya, S.

  Gordon Research Conference: Mechanisms of Cell Signaling, Aug. 2011, English, Lewiston, ME, United States, International conference

  Poster presentation

• Elucidation of neural circuit mechanisms underlying diversity in behavioral changes induced by chronic stress

  Ryota Shinohara

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Grant-in-Aid for Scientific Research (C), Kobe University, Apr. 2022 - Mar. 2025


• Elucidation of the molecular and neural circuit basis of individual differences in stress resilience

  Ryota Shinohara

  Japan Agency for Medical Research and Development (AMED), Advanced Research & Development Programs for Medical Innovation (PRIME), Kobe University, Oct. 2021 - Mar. 2025, Principal investigator


• Elucidation of the neural basis underlying individual differences in brain dysfunction caused by chronic stress

  The Sumitomo Foundation, Grant for Basic Science Research Projects, Kobe University, 2021 - 2022, Principal investigator


• Molecular and neural circuit mechanisms underlying rapid antidepressant actions

  The Uehara Memorial Foundation, Research Fellowship, Yale University, Sep. 2017 - Aug. 2019, Principal investigator


• Identifying the molecular and neural circuit mechanisms of the action of rapid-acting antidepressants

  National Institute for Physiological Sciences, Japan-U.S. Brain Research Cooperation Program, Yale University, Sep. 2017 - Mar. 2018, Principal investigator


• ドパミン受容体を介した前頭前皮質の神経回路成熟と情動制御での役割

  SHINOHARA Ryota

  Japan Society for the Promotion of Science, Grant-in-Aid for Young Scientists (B), Apr. 2016 - Mar. 2018, Principal investigator

  Competitive research funding


• 慢性ストレスによる前頭前皮質の機能変化の分子基盤とその役割

  SHINOHARA Ryota

  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research, Apr. 2013 - Mar. 2016, Principal investigator

  Competitive research funding


• 神経発生におけるRho標的分子mDiaの役割

  SHINOHARA Ryota

  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research, Apr. 2010 - Mar. 2012, Principal investigator

  Competitive research funding

• 心理的不調を予防又は緩和するための剤

  特願2023-74915, 28 Apr. 2023

  Patent right