Laboratoire de Physiologie Cérébrale, Université Paris Descartes and Centre National de la Recherche Scientifique, CNRS UMR8118, Paris, France.
Current affiliation: INSERM U1127, CNRS UMR 7225, Sorbonne Universités, UPMC Université Paris 06 UMRS 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
J Physiol. 2017 Dec 15;595(24):7477-7493. doi: 10.1113/JP275369. Epub 2017 Nov 21.
GABA receptors have been described in the axonal compartment of neurons; contrary to dendritic GABA receptors, axonal GABA receptors usually induce depolarizing responses. In this study we describe the presence of functional axonal GABA receptors in cerebellar Purkinje cells by using a combination of direct patch-clamp recordings from the axon terminals and laser GABA photolysis. In Purkinje cells, axonal GABA receptors are depolarizing and induce an increase in neurotransmitter release that results in a change of short-term synaptic plasticity. These results contribute to our understanding of the cellular mechanisms of action of axonal GABA receptors and highlight the importance of the presynaptic compartment in neuronal computation.
In neurons of the adult brain, somatodendritic GABA receptors (GABA Rs) mediate fast synaptic inhibition and play a crucial role in synaptic integration. GABA Rs are not only present in the somatodendritic compartment, but also in the axonal compartment where they modulate action potential (AP) propagation and transmitter release. Although presynaptic GABA Rs have been reported in various brain regions, their mechanisms of action and physiological roles remain obscure, particularly at GABAergic boutons. Here, using a combination of direct whole-bouton or perforated patch-clamp recordings and local GABA photolysis in single axonal varicosities of cerebellar Purkinje cells, we investigate the subcellular localization and functional role of axonal GABA Rs both in primary cultures and acute slices. Our results indicate that presynaptic terminals of PCs carry GABA Rs that behave as auto-receptors; their activation leads to a depolarization of the terminal membrane after an AP due to the relatively high cytoplasmic Cl concentration in the axon, but they do not modulate the AP itself. Paired recordings from different terminals of the same axon show that the GABA R-mediated local depolarizations propagate substantially to neighbouring varicosities. Finally, the depolarization mediated by presynaptic GABA R activation augmented Ca influx and transmitter release, resulting in a marked effect on short-term plasticity. Altogether, our results reveal a mechanism by which presynaptic GABA Rs influence neuronal computation.
GABA 受体已在神经元的轴突区被描述；与树突 GABA 受体相反，轴突 GABA 受体通常诱导去极化反应。在这项研究中，我们通过直接从轴突末梢进行膜片钳记录和激光 GABA 光解的组合，描述了小脑浦肯野细胞中功能性轴突 GABA 受体的存在。在浦肯野细胞中，轴突 GABA 受体去极化，并诱导神经递质释放增加，从而导致短期突触可塑性的变化。这些结果有助于我们理解轴突 GABA 受体的细胞作用机制，并强调了突触前区在神经元计算中的重要性。
在成年大脑的神经元中，体树突 GABA 受体（GABA Rs）介导快速突触抑制，并在突触整合中发挥关键作用。GABA Rs 不仅存在于体树突区，而且还存在于轴突区，在那里它们调节动作电位（AP）的传播和递质的释放。尽管在各种脑区都报道了突触前 GABA Rs，但它们的作用机制和生理作用仍然不清楚，特别是在 GABA 能末梢。在这里，我们使用直接全末梢或穿孔膜片钳记录和单个小脑浦肯野细胞轴突的局部 GABA 光解的组合，在原代培养物和急性切片中研究了轴突 GABA Rs 的亚细胞定位和功能作用。我们的结果表明，PC 的突触前末梢携带 GABA Rs，其行为为自受体；由于轴突中相对较高的细胞质 Cl 浓度，它们在 AP 后导致末梢膜的去极化，但它们本身不调节 AP。来自同一轴突的不同末梢的成对记录表明，GABA R 介导的局部去极化可实质传播到邻近的膨体。最后，突触前 GABA R 激活介导的去极化增加了 Ca 内流和递质释放，从而对短期可塑性产生了显著影响。总之，我们的结果揭示了突触前 GABA Rs 影响神经元计算的一种机制。
