Frequency-dependent depression of excitatory synaptic transmission is independent of activation of MCPG-sensitive presynaptic metabotropic glutamate receptors in cultured hippocampal neurons.
Frequency-dependent depression of excitatory synaptic transmission is independent of activation of MCPG-sensitive presynaptic metabotropic glutamate receptors in cultured hippocampal neurons.
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兴奋性突触传递的频率依赖性抑制与培养的海马神经元中 MCPG 敏感的突触前代谢型谷氨酸受体的激活无关。
DOI：
10.1152/jn.1995.74.4.1671
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Dichter,MA
中科院分区：
文献类型：
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作者：
Maki,R;Cummings,DD;Dichter,MA
1.采用成对脉冲范式和高频序列加测试脉冲来研究突触前代谢性谷氨酸受体（mGluRs）在兴奋性突触后电流（EPSC）振幅的频率依赖性调制中可能发挥的作用。使用mGluR拮抗剂（RS）-α-甲基-4-羧基苯甘氨酸（MCPG，500 μ M）和mGluR激动剂（1 S，3R）-1-氨基环戊烷-1，3-二羧酸[（1 S，3R）-ACPD，100 μ M]，对维持在极低密度培养物中的单突触连接海马神经元进行配对全细胞膜片钳记录。2.配对脉冲抑制（PPD）中观察到的所有兴奋对记录。平均PPD比（第2个EPSC的振幅除以第1个EPSC的振幅）为0.80 +/- 0.1（SD）（n = 8）。应用mGluR拮抗剂MCPG对EPSC的振幅没有影响，也没有影响两种EPSC的比率（PPD比率为0.79 +/- 0.2）。3.在4 mM细胞外Ca 2+（n = 5）和1 mM细胞外Ca 2+（n = 6）中，以高频率（20 Hz）刺激的10个连续EPSC的幅度平均递减。在所有测试对中，观察到强直后抑郁（PTD）（PTD比0.7 +/- 0.2）。浴应用MCPG（500 μ M）没有影响的幅度的EPSC在列车; MCPG也没有影响PTD。4. mGluR激动剂（1 S，3R）-ACPD在成对脉冲（第一EPSC，35 +/- 9%;第二EPSC，36 +/- 10%）和强直后脉冲（1和4 mM细胞外Ca 2+）模式中均降低了EPSC的振幅。观察到的抑郁程度（PPD和PTD）不受（1 S，3R）-ACPD应用的影响。拮抗剂MCPG（500 μ M）的共同应用阻断了（1 S，3R）-ACPD（100 μ M）的作用。5.我们的结论是，频率依赖性抑郁症的EPSC振幅发生独立的内源性激活的MCPG敏感的mGluRs在培养的海马神经元。此外，我们证明，外源性激活mGluRs的激动剂（1 S，3R）-ACPD可以产生额外的EPSC抑郁症以上，已经存在的频率依赖性机制。
1. A paired-pulse paradigm, and a high-frequency train followed by a test pulse, were used to investigate the possible role of presynaptic metabotropic glutamate receptors (mGluRs) in frequency-dependent modulation of the amplitude of excitatory post-synaptic currents (EPSCs). Paired whole cell patch-clamp recordings from monosynaptically connected hippocampal neurons maintained in very low-density cultures were performed, using the mGluR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM) and the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD, 100 microM]. 2. Paired-pulse depression (PPD) was observed in all the excitatory pairs recorded. The average PPD ratio (amplitude of the 2nd EPSC divided by the amplitude of the 1st EPSC) was 0.80 +/- 0.1 (SD) (n = 8). Application of the mGluR antagonist MCPG had no effect on the amplitude of the EPSCs and did not affect the ratio of the two EPSCs (PPD ratio 0.79 +/- 0.2). 3. The amplitudes of 10 successive EPSCs stimulated at a high frequency (20 Hz) decremented on average in both 4 mM extracellular Ca2+ (n = 5) and in 1 mM extracellular Ca2+ (n = 6). In all pairs tested, posttetanic depression (PTD) was observed (PTD ratio 0.7 +/- 0.2). Bath application of MCPG (500 microM) did not affect the amplitudes of the EPSCs during the train; MCPG also did not affect PTD. 4. The mGluR agonist (1S,3R)-ACPD depressed the amplitudes of the EPSCs in both the paired-pulse (1st EPSC, 35 +/- 9%; 2nd EPSC, 36 +/- 10%) and posttetanic pulse (1 and 4 mM extracellular Ca2+) paradigms. The amount of depression observed, both PPD and PTD, remained unaffected by application of (1S,3R)-ACPD. Coapplication of the antagonist MCPG (500 microM) blocked the effects of (1S,3R)-ACPD (100 microM). 5. We conclude that frequency-dependent depression of EPSC amplitudes occurs independent of endogenous activation of MCPG-sensitive mGluRs in cultured hippocampal neurons. Moreover, we demonstrate that exogenous activation of mGluRs by the agonist (1S,3R)-ACPD can produce additional EPSC depression above that already present due to frequency-dependent mechanisms.