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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Distinguishing between presynaptic and postsynaptic mechanisms of short-term depression during action potential trains.
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Distinguishing between presynaptic and postsynaptic mechanisms of short-term depression during action potential trains.

机译：区分动作电位训练期间短期抑郁的突触前和突触后机制。

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摘要

Short-term facilitation and depression have a profound influence on transmission at many glutamatergic synapses, particularly during trains of stimuli. A major component of these processes is postsynaptic receptor desensitization. Both presynaptic and postsynaptic mechanisms can contribute to synaptic efficacy, but it is often difficult to define their respective contributions. Blockers of desensitization such as cyclothiazide (CTZ) can be used, but many of these drugs have nonspecific effects on transmitter release, complicating attempts to define synaptic effectiveness under physiological conditions. We describe and validate a new method to minimize desensitization during trains of synaptic stimuli that is based on the low-affinity competitive glutamate receptor antagonists gamma-D-glutamylglycine or kynurenic acid. A computational model of AMPA receptor kinetics shows that the mechanism can be accounted for by simple competitive antagonism of AMPA receptors, where the rapid off-rate of the antagonist permits re-equilibration between blocked and unblocked pools during the interstimulus interval. Our results at the calyx of Held show that desensitization makes little contribution to synaptic depression at frequencies below 10 Hz, but at higher frequencies it makes an important contribution, with accumulating desensitization masking short-term facilitation and causing an underestimation of quantal content. This novel method of protection from desensitization is compatible with physiological studies but cannot be used in conjunction with CTZ. Although presynaptic vesicle depletion makes the dominant contribution to short-term depression, our results show that AMPA receptor desensitization contributes to the depression at auditory synapses after hearing onset and in a frequency-dependent manner.
机译：短期促进和抑郁对许多谷氨酸能突触的传递有深远的影响，特别是在刺激过程中。这些过程的主要成分是突触后受体脱敏。突触前和突触后机制均可促进突触效力，但通常很难定义其各自的作用。可以使用脱敏阻滞剂，例如环噻嗪（CTZ），但其中许多药物对递质释放具有非特异性作用，使在生理条件下定义突触有效性的尝试变得复杂。我们描述并验证一种新的方法，以使基于低亲和力竞争性谷氨酸受体拮抗剂γ-D-谷氨酰胺基甘氨酸或犬尿酸的突触刺激序列最小化脱敏。 AMPA受体动力学的计算模型表明，该机理可以由AMPA受体的简单竞争性拮抗来解释，其中拮抗剂的快速解离速率允许在刺激间隔期间阻滞和未阻滞池之间重新平衡。我们在Held花萼中的结果表明，在低于10 Hz的频率下，脱敏对突触抑制作用不大，但是在较高频率下，脱敏作用却很重要，因为脱敏作用的累积掩盖了短期的促进作用，并导致定量含量的低估。这种保护脱敏的新方法与生理学研究兼容，但不能与CTZ结合使用。尽管突触前囊泡耗竭是短期抑郁症的主要因素，但我们的研究结果表明，AMPA受体的脱敏作用是在听力发作后以频率依赖性的方式促进听觉突触中的抑郁症。

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