GABA(A)受容体過剰発現マウスにおけるシナプス可塑性

• Project/Area Number: 18709005
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Neuroscience in general
• Research Institution: Osaka University
• Principal Investigator: 豊田 博紀 Osaka University, 大学院・歯学研究科, 講師 (00432451)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 2007: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
• Keywords: GABA / PRIP / バレル皮質 / 側方抑制 / 脱感作

Research Abstract

PRIP-1/2分子はGABA(A)受容体の膜輸送(エクソサイトーシスおよびエンドサイトーシス)に関与し、GABA(A)受容体の膜への発現量を調節していると考えられ、その結果としてGABA(A)受容体作用を変化させ、シナプス可塑性に影響を与える可能性が示唆される。これまでの研究により、PRIP-1/2分子のダブルノックアウトマウス(DKO)マウスでは野生型に比して脱感作が顕著に観察されることを明らかにしてきたため、本年度は、脱感作について詳細な解析を行った。
1.DKOマウスにおける二連GABAパフ投与時のGABA(A)受容体電流
GABAの二連パフ投与の投与間隔を短縮することにより脱感作を強化した際、GABA(A)受容体電流の脱感作が増強するのに伴いテール電流が大きくなることを観察した。
2.DKOマウスにおけるGABA(A)受容体電流に対するNipecotic acidの影響
GABAの取込阻害薬であるNipecotic acid(1mM)投与後、GABA(A)受容体の脱感作が進行するのに伴いテール電流の再活性化の割合が増大することが明らかとなった。
3.DKOマウスにおけるGABA(A)受容体電流に対するに対する細胞外カルシウム濃度の影響
細胞外カルシウム濃度を1mMから2.5mMに上昇することにより、脱感作の進行およびそれに伴うテール電流の出現及び増強が観察された。
DKOマウスでのこうしたGABA(A)受容体チャネルの特性が、シナプス可塑性に影響を与える可能性が示唆された。

Research Products

• [Journal Article] Differential columnar processing in local circuits of barrel and insular cortex (2008)
  • Author(s): Sato H., et. al.
  • Journal Title: The Journal of Neuroscience in press
  • Peer Reviewed
• [Journal Article] Requirement of extracellular signal-regulated kinase/mitogen-activated protein kinase for long-term potentiation in adult mouse anterior cingulate cortex (2007)
  • Author(s): Toyoda H., et. al.
  • Journal Title: Molecular Pain 3 Pages: 36-36
  • Peer Reviewed
• [Journal Article] Nitric oxide activates leak K+ currents in the presumed cholinergic neuron of basal forebrain (2007)
  • Author(s): Kang Y., et. al.
  • Journal Title: Journal of Neurophysiology 98 Pages: 3397-3410
  • Peer Reviewed
• [Journal Article] Alteration of cingulate long-term plasticity and behavioral sensitization to inflam mation by environmental enrichment (2007)
  • Author(s): Shum F.W., et. al.
  • Journal Title: Learning and Memory 14 Pages: 304-312
  • Peer Reviewed
• [Journal Article] Long-term depression requires postsynaptic AMPA GluR2 receptor in adult mouse cingulate cortex (2007)
  • Author(s): Toyoda H., et. al.
  • Journal Title: Journal of Cellular Physiology 211 Pages: 336-343
  • Peer Reviewed
• [Journal Article] Involvement of persistent Na+ current in spike initiation in primary sensory neurons of the rat mesencephalic trigeminal nucleus (2007)
  • Author(s): Kang Y., et. al.
  • Journal Title: Journal of Neurophysiology 97 Pages: 2385-2393
  • Peer Reviewed
• [Journal Article] Time-dependent postsynaptic AMPA GluR1 receptor recruitment in the cingulate synaptic potentiation (2007)
  • Author(s): Toyoda H. et al.
  • Journal Title: Developmental Neurobiology 67 Pages: 498-509
• [Journal Article] Increased anxiety-like behavior and enhanced synaptic efficacy in the amygdala of GluR5 knockout mice (2007)
  • Author(s): Wu L.J.et al.
  • Journal Title: Public Library of Science One 2
• [Journal Article] Genetic evidence for adenylyl cyclase 1 as a target for preventing neuronal excitotoxicity mediated by N-methyl-D-aspartate receptors (2007)
  • Author(s): Wang H.et al.
  • Journal Title: Journal of biological chemistry 282 Pages: 1507-1517
• [Journal Article] NMDA receptor dependent long-term depression in anterior cingulate cortex (2006)
  • Author(s): Toyoda H. et al.
  • Journal Title: Reviews in the Neurosciences 17 Pages: 403-413
• [Journal Article] Enhanced presynaptic neurotransmitter release in the anterior cingulate cortex of the mice with chronic pain (2006)
  • Author(s): Zhao M.G.et al.
  • Journal Title: Journal of Neuroscience 26 Pages: 8923-8930
• [Journal Article] Neuromedin U receptor 2 deficient mice display differential responses in sensory perception, stress and feeding (2006)
  • Author(s): Zeng H.et al.
  • Journal Title: Mollecular and Cellular Biology 26 Pages: 9352-9363
• [Journal Article] Presynaptic regulation of the inhibitory transmission by GluR5-containing kainate receptors in spinal substantia gelatinosa (2006)
  • Author(s): Xu H.et al.
  • Journal Title: Molecular Pain 2 Pages: 29-29
• [Journal Article] Evidence for a role of CaMKIV in the development of opioid analgesic tolerance (2006)
  • Author(s): Ko S.W.et al.
  • Journal Title: European Journal of Neuroscience 23 Pages: 2158-2168
• [Presentation] GABA作動性シナプス後電流を修飾するPRIP分子の役割 (2007)
  • Author(s): 豊田, et. al.
  • Organizer: 第30回日本神経科学大会
  • Place of Presentation: 横浜
• [Presentation] Phospholipase C-related catalytically inactive prtein (PRIP) regulates GABA_A responses in the barrel cortex (2007)
  • Author(s): Hiral K., et. al.
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, USA