Mechanisms underlying control of developmental plasticity by glutamate receptros of NMDA type

NMDA 型谷氨酸受体控制发育可塑性的机制

• 批准号: 01480125
• 负责人: TSUMOTO Tadaharu
• 金额: $ 4.29万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-01480125/
• 关键词: NMDA receptor; Glutamate receptor; Synaptic plasticity; Visual cortex; Long-term potentiation; Long-term depression; Development; Rat; グルタミン酸受溶体; 発達脳; 大脳皮質; グルタミン酸; カルシウム

Long-term potentiation (LTP) of synaptic efficacy is a well known example of a use-dependent synaptic plasticity in the mammalian brain. In the developing visual cortex In particular, LTP is proposed as a basis of environmental modifiability of visual cortical neurons during a "critical period" of postnatal development. Previous studies suggested that glutamate receptors of N-methyl-D-aspartate (NMDA) type may play a role in induction of LTP and an entry of Ca^<2+> into postsynaptic sites through NMDA receptor-linked channels may trigger processes for induction of LTP. However, there were no direct experimental data supporting this hypothesis in the developing visual cortex. In the present study, therefore, we attempted to test this hypothesis and found that the induction of LTP is blocked by the application of an NMDA receptor antagonist and further that an injection of a Ca^<2+>-chelator into visual cortical neurons leads to long-term depression (LTD) of their excitatory postsynaptic potentials (EPSPs) following tetanic afferent stimuli which in most of the slices tested, simultaneously induce LTP of field potentials derived from unchelated cells. These results suggest that the low concentration of postsynaptic, free Ca^<22+> associated which tetanic synaptic inputs may lead to LTD while a rise of Ca^<2+> through activated NMDA receptor-linked channels may lead to LTP.

突触功效的长时程增强（LTP）是哺乳动物大脑中依赖于使用的突触可塑性的一个众所周知的例子。特别是在发育中的视觉皮层中，LTP被认为是出生后发育“关键时期”视觉皮层神经元环境可改变性的基础。先前的研究表明，N-甲基-D-天冬氨酸(NMDA)型谷氨酸受体可能在LTP的诱导中发挥作用，并且Ca^2+通过NMDA受体连接通道进入突触后位点可能触发诱导过程。的LTP。然而，在发育中的视觉皮层中没有直接的实验数据支持这一假设。因此，在本研究中，我们试图检验这一假设，发现 LTP 的诱导被 NMDA 受体拮抗剂的应用所阻断，并且进一步将 Ca ^ 2+ -螯合剂注射到视觉皮层神经元中导致 LTP 的诱导。强直性传入刺激后其兴奋性突触后电位（EPSP）的长期抑制（LTD），在大多数测试的切片中，同时诱导来自未螯合细胞的场电位的 LTP。这些结果表明与破伤风突触输入相关的低浓度突触后游离Ca 22+ 可能导致LTD，而通过激活的NMDA受体连接通道的Ca 22+ 升高可能导致LTP。

项目成果

Yoshimura,Y.et al.: "Inputーspecific induction of longーterm depression in Ca^<2+>ーchelated visual cortex neurons." NeuroReport.

Yoshimura, Y. 等人：“Ca^2+ 螯合视觉皮层神经元的输入特异性诱导长期抑制。”

Kimura,F.et al.: "Longーterm potentiation and NーmethylーDーaspartate receptors in the visual cortex of young rats." Journal of physiology,London. 414. 125-149 (1989)

Kimura, F. 等人：“幼鼠视觉皮层的长时程增强和 N-甲基-D-天冬氨酸受体。” 生理学杂志，伦敦 414. 125-149 (1989)

Kimura,F.et al.: "Long-term potentiation and N-methyl-D-aspartate receptors in the visual cortex of young rats." Journal of Physiology,London.414. 125-149 (1989)

Kimura,F.等人：“幼鼠视觉皮层的长时程增强和 N-甲基-D-天冬氨酸受体。”

T.Tsumoto et al.: "A role of NMDA receptors and Ca^<2+> influx in synaptic plasticity in the developing visual cortex." Excitatory Amino Acid and Neuronal Plasticity(ed.by Ben-Ari,T.),Plenum Press. (1990)

T.Tsumoto 等人：“NMDA 受体和 Ca^2 流入在发育中的视觉皮层突触可塑性中的作用。”

Shirokawa, T., Nishigori, A. Kimura, F. and Tsumoto, T.: "Actions of excitatory amino acid antagonists on synaptic potentials of layer II/III neurons of the cat visual cortex." Exp. Brain Res.78. 489-500 (1989)

Shirokawa, T.、Nishigori, A. Kimura, F. 和 Tsumoto, T.：“兴奋性氨基酸拮抗剂对猫视觉皮层 II/III 层神经元突触电位的作用。”