Involvement of AMPA receptor desensitization in short-term synaptic depression at the calyx of Held in developing rats

Involvement of AMPA receptor desensitization in short-term synaptic depression at the calyx of Held in developing rats
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DOI:
10.1113/jphysiol.2007.142547
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发表时间:
2008-05-01
影响因子:
5.5
通讯作者:
Takahashi, Tomoyuki
Takahashi, Tomoyuki
中科院分区:
医学1区
文献类型:
--
作者:
Koike-Tani, Maki;Kanda, Takeshi;Takahashi, Tomoyuki

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成对脉冲易化(PPF)和抑郁(PPD)是短期可塑性的形式,通常被认为反映了递质释放概率的变化。然而,突触后AMPA受体(AMPAR)的脱敏显着有助于PPD在许多突触能突触。为了澄清参与突触PPD的AMPAR脱敏,我们比较PPD与AMPAR脱敏,诱导成对脉冲谷氨酸应用程序中的补丁从突触后细胞在发育中的大鼠举行突触的萼。我们发现,AMPAR脱敏在听力开始前(P10-12)对PPD有显著贡献,但在听力开始后,其贡献变得微不足道。在出生后发育期间(P7-21),AMPAR从脱敏中恢复得更快。AMPAR脱敏的谷氨酸敏感性降低。单细胞逆转录-聚合酶链反应(RT-PCR)分析表明GluR 1表达的发育下降与AMPAR从脱敏中恢复的速度有关。在出生后第二周(P7-14),递质释放概率下降。操纵细胞外Ca 2 +/Mg 2+比率,以匹配P7-8和P13-15突触的释放概率,揭示了释放概率也是决定PPD中AMPAR脱敏参与的重要因素。我们的结论是,参与AMPAR脱敏在短期突触抑制的程度是由突触前和突触后机制。
Paired-pulse facilitation (PPF) and depression (PPD) are forms of short-term plasticity that are generally thought to reflect changes in transmitter release probability. However, desensitization of postsynaptic AMPA receptors (AMPARs) significantly contributes to PPD at many glutamatergic synapses. To clarify the involvement of AMPAR desensitization in synaptic PPD, we compared PPD with AMPAR desensitization, induced by paired-pulse glutamate application in patches excised from postsynaptic cells at the calyx of Held synapse of developing rats. We found that AMPAR desensitization contributed significantly to PPD before the onset of hearing (P10-12), but that its contribution became negligible after hearing onset. During postnatal development (P7-21) the recovery of AMPARs from desensitization became faster. Concomitantly, glutamate sensitivity of AMPAR desensitization declined. Single-cell reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated a developmental decline of GluR1 expression that correlated with speeding of the recovery of AMPARs from desensitization. Transmitter release probability declined during the second postnatal week (P7-14). Manipulation of the extracellular Ca2+/Mg2+ ratio, to match release probability at P7-8 and P13-15 synapses, revealed that the release probability is also an important factor determining the involvement of AMPAR desensitization in PPD. We conclude that the extent of involvement of AMPAR desensitization in short-term synaptic depression is determined by both pre- and postsynaptic mechanisms.