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J Physiol. 2017 Dec 15;595(24):7477-7493. doi: 10.1113/JP275369. Epub 2017 Nov 21.

Axonal GABAA receptors depolarize presynaptic terminals and facilitate transmitter release in cerebellar Purkinje cells.

Author information

1
Laboratoire de Physiologie Cérébrale, Université Paris Descartes and Centre National de la Recherche Scientifique, CNRS UMR8118, Paris, France.
2
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.
3
Graduate School of Brain Science, Doshisha University, Kyotanabe, Kyoto, Japan.
4
Society-Academia Collaboration for Innovation, Kyoto University, Sakyo-ku, Kyoto, 606-8501, Japan.
5
Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.

Abstract

KEY POINTS:

GABAA receptors have been described in the axonal compartment of neurons; contrary to dendritic GABAA receptors, axonal GABAA receptors usually induce depolarizing responses. In this study we describe the presence of functional axonal GABAA 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 GABAA 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 GABAA receptors and highlight the importance of the presynaptic compartment in neuronal computation.

ABSTRACT:

In neurons of the adult brain, somatodendritic GABAA receptors (GABAA Rs) mediate fast synaptic inhibition and play a crucial role in synaptic integration. GABAA 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 GABAA 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 GABAA Rs both in primary cultures and acute slices. Our results indicate that presynaptic terminals of PCs carry GABAA 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 GABAA R-mediated local depolarizations propagate substantially to neighbouring varicosities. Finally, the depolarization mediated by presynaptic GABAA R activation augmented Ca2+ influx and transmitter release, resulting in a marked effect on short-term plasticity. Altogether, our results reveal a mechanism by which presynaptic GABAA Rs influence neuronal computation.

KEYWORDS:

GABA receptor; Purkinje cells; cerebellum; direct recording; presynaptic terminal; synaptic transmission

PMID:
29072780
PMCID:
PMC5730858
DOI:
10.1113/JP275369
[Indexed for MEDLINE]
Free PMC Article

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