Alcami Pepe
Laboratoire de Physiologie Cérébrale, Unité Mixte de Recherche UMR8118, Université Paris Descartes and Centre National de la Recherche Scientifique, Paris, France.
Laboratory of Cellular and Systemic Neurophysiology, Institute for Physiology I, Albert-Ludwigs University Freiburg, Freiburg, Germany.
Front Cell Neurosci. 2018 Jun 19;12:156. doi: 10.3389/fncel.2018.00156. eCollection 2018.
Electrical synapses are ubiquitous in interneuron networks. They form intercellular pathways, allowing electrical currents to leak between coupled interneurons. I explored the impact of electrical coupling on the integration of excitatory signals and on the coincidence detection abilities of electrically-coupled cerebellar basket cells (BCs). In order to do so, I quantified the influence of electrical coupling on the rate, the probability and the latency at which BCs generate action potentials when stimulated. The long-lasting simultaneous suprathreshold depolarization of a coupled cell evoked an increase in firing rate and a shortening of action potential latency in a reference basket cell, compared to its depolarization alone. Likewise, the action potential probability of coupled cells was strongly increased when they were simultaneously stimulated with trains of short-duration near-threshold current pulses (mimicking the activation of presynaptic granule cells) at 10 Hz, and to a lesser extent at 50 Hz, an effect that was absent in non-coupled cells. Moreover, action potential probability was increased and action potential latency was shortened in response to synaptic stimulations in mice lacking the protein that forms gap junctions between BCs, connexin36, relative to wild-type (WT) controls. These results suggest that electrical synapses between BCs decrease the probability and increase the latency of stimulus-triggered action potentials, both effects being reverted upon simultaneous excitation of coupled cells. Interestingly, varying the delay at which coupled cells are stimulated revealed that the probability and the speed of action potential generation are facilitated maximally when a basket cell is stimulated shortly after a coupled cell. These findings suggest that electrically-coupled interneurons behave as coincidence and sequence detectors that dynamically regulate the latency and the strength of inhibition onto postsynaptic targets depending on the degree of input synchrony in the coupled interneuron network.
电突触在中间神经元网络中普遍存在。它们形成细胞间通路,使电流在耦合的中间神经元之间泄漏。我探讨了电耦合对兴奋性信号整合以及对电耦合小脑篮状细胞(BCs)的同步检测能力的影响。为了做到这一点,我量化了电耦合对BCs在受到刺激时产生动作电位的频率、概率和潜伏期的影响。与单独去极化相比,耦合细胞的长时间同时超阈值去极化会引起参考篮状细胞放电频率增加和动作电位潜伏期缩短。同样,当耦合细胞在10 Hz时用短持续时间近阈值电流脉冲串(模拟突触前颗粒细胞的激活)同时刺激时,动作电位概率大幅增加,在50 Hz时增加程度较小,而在非耦合细胞中不存在这种效应。此外,相对于野生型(WT)对照,在缺乏形成BCs之间缝隙连接的蛋白连接蛋白36的小鼠中,对突触刺激的反应中动作电位概率增加且动作电位潜伏期缩短。这些结果表明,BCs之间的电突触降低了刺激触发动作电位的概率并增加了潜伏期,而在耦合细胞同时兴奋时这两种效应都会逆转。有趣的是,改变耦合细胞受到刺激的延迟时间发现,当一个篮状细胞在耦合细胞之后不久受到刺激时,动作电位产生的概率和速度得到最大程度的促进。这些发现表明,电耦合的中间神经元起到同步和序列检测器的作用,根据耦合中间神经元网络中的输入同步程度动态调节对突触后靶标的抑制潜伏期和强度。