Mechanisms of anorectic hormone-induced gustatory regulation in the cerebral cortex

• Project/Area Number: 25293379
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Nihon University
• Principal Investigator: KOBAYASHI Masayuki 日本大学, 歯学部, 准教授 (00300830)
• Co-Investigator(Kenkyū-buntansha): CUI Yelong 理化学研究所, ライフサイエンス技術基盤研究センター, ユニットリーダー (60312229) ; INUI Tadashi 大阪大学, 大学院人間科学研究科, 助教 (40324735)
• Co-Investigator(Renkei-kenkyūsha): MIZOGUCHI Naoko 明海大学, 歯学部, 助教 (00548919) ; YAMAMOTO Kiyofumi 日本大学, 歯学部, 助教 (30609764)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2015: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2014: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000); Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 島皮質 / 味覚 / レプチン / 局所回路 / 大脳皮質 / 摂食関連ホルモン / 光学計測 / パッチクランプ / 口腔感覚 / 抑制性シナプス後電流 / 興奮性シナプス後電流 / セカンドメッセンジャー / PI3K / JAK2/STAT3

Outline of Final Research Achievements

Leptin plays a pivotal role in regulation of energy balance by controlling appetite and metabolism. The insular cortex (IC) processes gustatory and visceral information, which functionally correlate to feeding behavior. However, it is still an open issue how leptin modulates synaptic transmission in the IC and other cortical areas. We recorded excitatory propagation by an optical imaging technique using in vivo preparations. Leptin effectively suppressed the amplitude and area of excitatory propagation in the IC. Paired whole-cell patch-clamp recordings from pyramidal and fast-spiking cells were performed using rat IC slice preparations to explore the mechanisms of leptin-induced suppression of excitatory propagation. Leptin reciprocally modulated uEPSCs and uIPSCs via presynaptic mechanisms, and as a whole, leptin suppresses neural excitability in the IC. Leptin-induced suppression of excitation may contribute the refinement of cortico-cortical information processing of gustation.

Research Products

• [Journal Article] Sequential Changes in Cortical Excitation during Orthodontic Treatment. (2016)
  • Author(s): Horinuki E, Yamamoto K, Shimizu N, Koshikawa N, Kobayashi M.
  • Journal Title: J Dent Res Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Distinct Excitation to Pulpal Stimuli between Somatosensory and Insular Cortices. (2016)
  • Author(s): Nakamura H, Shirakawa T, Koshikawa N, Kobayashi M.
  • Journal Title: J Dent Res Volume: 95 Issue: 2 Pages: 180-7
  • DOI: 10.1177/0022034515611047
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Cytoarchitecture-dependent decrease in propagation velocity of cortical spreading depression in the rat insular cortex revealed by optical imaging. (2016)
  • Author(s): Fujita S., Mizoguchi N., Aoki R., Cui, Y.L., Koshikawa N., and Kobayashi M
  • Journal Title: Cerebral Cortex Volume: 26 Issue: 4 Pages: 1580-1589
  • DOI: 10.1093/cercor/bhu336
  • Peer Reviewed
• [Journal Article] Involvement of medullary GABAergic system in extraterritorial neuropathic pain mechanisms associated with inferior alveolar nerve transection. (2015)
  • Author(s): Okada-Ogawa A, Nakaya Y, Imamura Y, Kobayashi M, Shinoda M, Kita K, Sessle BJ, Iwata K.
  • Journal Title: Experimental of Neurology Volume: 28 Pages: 42-52
  • DOI: 10.1016/j.expneurol.2015.02.030
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Presynaptic cell type-dependent regulation of GABAergic synaptic transmission by nitric oxide in rat insular cortex. (2015)
  • Author(s): Yamamoto K, Takei H, Koyanagi Y, Koshikawa N, Kobayashi M.
  • Journal Title: Neuroscience Volume: 284 Pages: 65-77
  • DOI: 10.1016/j.neuroscience.2014.09.062
  • Peer Reviewed / Open Access
• [Journal Article] Spatiotemporal profiles of dental pulp nociception in rat cerebral cortex: an optical imaging study. (2015)
  • Author(s): Nakamura H, Kato, R, Shirakawa T, Koshikawa N, Kobayashi M
  • Journal Title: Journal of Comparative Neurology Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Anisotropic propagation of spreading depression in different cortical regions of the rat. (2015)
  • Author(s): Fujita S, Mizoguchi N, Cui YL, Koshikawa N, Kobayashi M
  • Journal Title: Cereb Cortex Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Orthodontic force facilitates cortical responses to periodontal stimulation. (2015)
  • Author(s): Horinuki E, Shinoda M, Shimizu N, Koshikawa N, Kobayashi M
  • Journal Title: J Dent Res Volume: in press
  • Peer Reviewed
• [Journal Article] Fast-spiking cell to pyramidal cell connections are the most sensitive to propofol-induced facilitation of GABAergic currents in rat insular cortex.. (2014)
  • Author(s): Koyanagi Y, Oi Y, Yamamoto K, Koshikawa N, Kobayashi M
  • Journal Title: Anesthesiology Volume: in press
  • Peer Reviewed
• [Journal Article] Functional anatomy of gustation in the alert rat revealed by positron emission tomography (2013)
  • Author(s): Kobayashi, M., Cui, Y.L.., Sako, T., Sasabe, T., Mizoguchi, N., Wada, Y., Kataoka, Y., Koshikawa, N
  • Journal Title: J Neurosci Res Volume: 91 Issue: 10 Pages: 1363-1370
  • DOI: 10.1002/jnr.23252
  • Peer Reviewed
• [Journal Article] Phenotypic characterization of orofacial movement topography in mutants with disruption of amino acid mechanisms: glutamate N2A/B/D [GluRε1/2/4] subtypes and the GABA synthesizing enzyme GAD65 (2013)
  • Author(s): Katsunori Tomiyama, Risako Kato, Yaeko Hara, Masayuki Kobayashi, Masayoshi Mishina, Yuchio Yanagawa, Anthony Kinsella, Noriaki Koshikawa and John L. Waddington
  • Journal Title: Neuroscience Volume: 250 Pages: 743-754
  • DOI: 10.1016/j.neuroscience.2013.07.038
  • Peer Reviewed
• [Journal Article] Reciprocal regulation of inhibitory synaptic transmission by nicotinic and muscarinic receptors in rat nucleus accumbens shell. (2013)
  • Author(s): Yamamoto K, Ebihara K, Koshikawa N, Kobayashi M
  • Journal Title: J Physiol Volume: 591 Issue: 22 Pages: 5745-5763
  • DOI: 10.1113/jphysiol.2013.258558
  • Peer Reviewed
• [Presentation] ラット下歯槽神経切断による島皮質の局所回路の可塑的変化 (2015)
  • Author(s): 小林真之
  • Organizer: 第57回歯科基礎医学会サテライトシンポジウム
  • Place of Presentation: 朱鷺メッセ（新潟県，新潟市）
  • Year and Date: 2015-09-11
• [Presentation] In vivo光学計測によるラット島皮質歯髄応答ニューロンの時空間的特性の解析 (2014)
  • Author(s): 小林真之
  • Organizer: 第56回歯科基礎医学会サテライトシンポジウム
  • Place of Presentation: 福岡
  • Year and Date: 2014-09-26
  • Invited
• [Presentation] Functional mapping of excitatory synaptic inputs in the agranular insular cortex. (2013)
  • Author(s): Yamamoto K, Koshikawa N, Kobayashi M.
  • Organizer: 43rd Society for Neuroscience
  • Place of Presentation: San Diego，U.S.A
• [Presentation] Reciprocal regulation of inhibitory synaptic transmission by nicotinic and muscarinic receptors in rat nucleus accumbens shell. (2013)
  • Author(s): Ebihara K, Yamamoto K, Ueda K, Koshikawa N, Kobayashi M
  • Organizer: 43rd Society for Neuroscience
  • Place of Presentation: San Diego，U.S.A
• [Remarks] 日本大学歯学部薬理学講座
  • URL: http://www2.dent.nihon-u.ac.jp/g.pharmacology/