Université Paris Cité , Saints Pères Paris Institute for the Neurosciences, CNRS, Paris, France.
J Gen Physiol. 2023 May 1;155(5). doi: 10.1085/jgp.202213212. Epub 2023 Apr 3.
In central synapses, spontaneous transmitter release observed in the absence of action potential firing is often considered as a random process lacking time or space specificity. However, when studying miniature glutamatergic currents at cerebellar synapses between parallel fibers and molecular layer interneurons, we found that these currents were sometimes organized in bursts of events occurring at high frequency (about 30 Hz). Bursts displayed homogeneous quantal size amplitudes. Furthermore, in the presence of the desensitization inhibitor cyclothiazide, successive events within a burst displayed quantal amplitude occlusion. Based on these findings, we conclude that bursts originate in individual synapses. Bursts were enhanced by increasing either the external potassium concentration or the external calcium concentration, and they were strongly inhibited when blocking voltage-gated calcium channels by cadmium. Bursts were prevalent in elevated potassium concentration during the formation of the molecular layer but were infrequent later in development. Since postsynaptic AMPA receptors are largely calcium permeant in developing parallel fiber-interneuron synapses, we propose that bursts involve presynaptic calcium transients implicating presynaptic voltage-gated calcium channels, together with postsynaptic calcium transients implicating postsynaptic AMPA receptors. These simultaneous pre- and postsynaptic calcium transients may contribute to the formation and/or stabilization of synaptic connections.
在中枢突触中,在没有动作电位放电的情况下观察到的自发递质释放通常被认为是一种缺乏时间或空间特异性的随机过程。然而,当我们在小脑平行纤维和分子层中间神经元之间的谷氨酸能微小电流研究中发现,这些电流有时会以高频(约 30 Hz)发生的事件爆发形式组织起来。爆发显示出均匀的量子大小幅度。此外,在脱敏抑制剂环噻嗪存在的情况下,爆发内的连续事件显示出量子幅度封闭。基于这些发现,我们得出结论,爆发起源于单个突触。通过增加外钾浓度或外钙浓度可以增强爆发,而当用镉阻断电压门控钙通道时,爆发则强烈抑制。在分子层形成过程中,升高钾浓度时爆发更为常见,但在发育后期则不太常见。由于发育中的平行纤维-中间神经元突触中的突触后 AMPA 受体在很大程度上是钙通透的,我们提出爆发涉及到突触前钙瞬变,这与突触前电压门控钙通道有关,同时也涉及到突触后钙瞬变,这与突触后 AMPA 受体有关。这些同时的突触前和突触后钙瞬变可能有助于形成和/或稳定突触连接。