Presynaptic Depression at a Calyx Synapse: The Small Contribution of Metabotropic Glutamate Receptors
Presynaptic Depression at a Calyx Synapse: The Small Contribution of Metabotropic Glutamate Receptors
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DOI：
10.1523/jneurosci.17-21-08137.1997
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发表时间：
1997-11
期刊：
影响因子：
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通讯作者：
H. von Gersdorff;R. Schneggenburger;Sibylle Weis;E. Neher
中科院分区：
文献类型：
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作者：
H. von Gersdorff;R. Schneggenburger;Sibylle Weis;E. Neher
诱发的EPSC的突触抑制用范围从0.2到100 Hz的刺激频率在由大鼠脑干中的Held的萼形成的单个CNS突触处进行量化。半最大抑制发生在0.1 Hz，10 Hz和100 Hz刺激频率分别将EPSC振幅降低至其初始幅度的0.30%和0.10%。由10 Hz传入纤维刺激引起的抑郁恢复的时间常数为4.2秒。AMPA和NMDA受体介导的EPSC在1-5 Hz刺激频率下平行抑制，表明抑制是由减少谷氨酸释放的突触前机制诱导的。为了确定自身受体对抑郁症的作用，我们研究了代谢型谷氨酸受体（mGluR）激动剂（1 S，3S）-ACPD和l-AP 4的抑制作用，发现它们以剂量依赖的方式被（RS）-α-环丙基-4-膦酰基苯基甘氨酸（CPPG）逆转，CPPG是一种新型的mGluR竞争性拮抗剂。在300 μm时，CPPG可完全逆转α-AP_4和（1 S，3S）-ACPD的作用，但降低5-10 Hz仅引起1.6%的抑制。CPPG敏感的mGluRs，推测激活谷氨酸溢出生理突触传递过程中，因此有助于短期突触抑制的顺序只有10%。因此，我们认为，5-10 Hz传入纤维刺激Held突触萼引起的强烈抑制的主要机制是突触囊泡池耗尽。
Synaptic depression of evoked EPSCs was quantified with stimulation frequencies ranging from 0.2 to 100 Hz at the single CNS synapse formed by the calyx of Held in the rat brainstem. Half-maximal depression occurred at ≈1 Hz, with 10 and 100 Hz stimulation frequencies reducing EPSC amplitudes to ≈30% and ≈10% of their initial magnitude, respectively. The time constant of recovery from depression elicited by 10 Hz afferent fiber stimulation was 4.2 sec. AMPA and NMDA receptor-mediated EPSCs depressed in parallel at 1–5 Hz stimulation frequencies, suggesting that depression was induced by presynaptic mechanism(s) that reduced glutamate release. To determine the contribution of autoreceptors to depression, we studied the inhibitory effects of the metabotropic glutamate receptor (mGluR) agonists (1S, 3S)-ACPD and l-AP4 and found them to be reversed in a dose-dependent manner by (RS)-α-cyclopropyl-4-phosphonophenylglycine (CPPG), a novel and potent competitive antagonist of mGluRs. At 300 μm, CPPG completely reversed the effects ofl-AP4 and (1S, 3S)-ACPD, but reduced 5–10 Hz elicited depression by only ≈6%. CPPG-sensitive mGluRs, presumably activated by glutamate spillover during physiological synaptic transmission, thus contribute on the order of only 10% to short-term synaptic depression. We therefore suggest that the main mechanism contributing to the robust depression elicited by 5–10 Hz afferent fiber stimulation of the calyx of Held synapse is synaptic vesicle pool depletion.