Requirement of rapid Ca2+ entry and synaptic activation of metabotropic glutamate receptors for the induction of long‐term depression in adult rat hippocampus
Requirement of rapid Ca2+ entry and synaptic activation of metabotropic glutamate receptors for the induction of long‐term depression in adult rat hippocampus
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DOI：
10.1111/j.1469-7793.1998.761bg.x
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发表时间：
1998-09
期刊：
影响因子：
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通讯作者：
S. Otani;J. Connor
中科院分区：
文献类型：
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作者：
S. Otani;J. Connor
1 在阻断 γ-氨基丁酸-A 介导的抑制过程中，对成年大鼠海马 Schaffer 侧支 CA1 神经元突触进行低频刺激（2 Hz，900 个脉冲）可诱导 N-甲基-D-天冬氨酸受体独立、突触后 Ca2+ 依赖性的突触强度抑制（长期抑制；LTD）。 2 使用 fura-2 进行比率成像显示，仅在 7.5 分钟刺激期的最初 约 30 秒内，树突 [Ca2+] 适度增加 (约 500 nM)。然而，30 秒的调节不足以诱导 LTD。 3 [Ca2+] 变化对代谢型谷氨酸受体 (mGluR) 拮抗剂 (+)-α-甲基-4-羧基苯基甘氨酸 (MCPG) 不敏感。然而，MCPG 在调节过程中完全阻断了 LTD。 4 [Ca2+] 变化被突触后超极化（胞体处 ‐110 mV）所消除。在调节过程中将神经元超极化至 ‐110 mV 会显着减弱 LTD 诱导。突触后蛋白激酶 C 抑制剂肽 PKC(19-36) 的存在也可阻断 5 LTD 诱导。 6 这些结果表明，通过长时间的低频刺激对成人海马体的 LTD 诱导取决于通过电压敏感通道的快速 Ca2+ 流入以及可能与磷脂酶 C 偶联的 mGluR 的突触刺激。
1 During block of γ‐aminobutyric acid‐A‐mediated inhibition, low‐frequency stimulation (2 Hz, 900 pulses) to Schaffer collateral‐CA1 neuron synapses of adult rat hippocampus induced an N‐methyl‐D‐aspartate receptor‐independent, postsynaptic Ca2+‐dependent depression of synaptic strength (long‐term depression; LTD). 2 Ratio imaging with fura‐2 revealed moderate dendritic [Ca2+] increases (≈500 nM) during only the initial ≈30 s of the 7.5 min stimulation period. Conditioning for 30 s was, however, insufficient to induce LTD. 3 The [Ca2+] changes were insensitive to the metabotropic glutamate receptor (mGluR) antagonist (+)‐α‐methyl‐4‐carboxyphenylglycine (MCPG). MCPG, however, completely blocked LTD when present during conditioning. 4 The [Ca2+] changes were abolished by postsynaptic hyperpolarization (‐110 mV at the soma). Hyperpolarizing neurons to ‐110 mV during conditioning significantly attenuated LTD induction. 5 LTD induction was also blocked by the postsynaptic presence of the protein kinase C inhibitor peptide PKC(19‐36). 6 These results suggest that LTD induction in adult hippocampus by prolonged low‐frequency stimulation depends on both a rapid Ca2+ influx through voltage‐sensitive channels and synaptic stimulation of mGluRs which may be coupled to phospholipase C.