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Séminaire impromptu - Marie GendrelGABAergic neurons in C. elegans: not so simple after all.

Abstract :

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the vertebrate brain and dysfunction of GABAergic neurons can have profound pathological implications.
The C. elegans nervous systemcan be considered as a “microcosm” of the GABA universe: smaller, simpler and experimentally more accessible than a vertebrate nervous system. Until recently, only 26 of the 302 neurons of C. elegans where thought to be GABAergic. These neurons fell into six classes based on their morphology and synaptic connectivity. They expressed all the components that classically define GABAergic neurons, also referred to as the GABAergic gene battery: (i) the enzyme responsible for GABA synthesis (GAD/unc-25), (ii) the GABA-specific vesicular transporter (VGAT/unc-47) and (iii) the GABA plasma membrane transporter (GAT/snf-11).

After extensive optimization of the anti-GABA immunostaining combined with expression pattern analysis of the GABAergic gene battery, I completely revised the classical view of GABAergic neurotransmission in C. elegans. In addition to the 26 “classical” GABA neurons, I identified 22 additional cells that were GABA positive. In particular, I found that neurons that contain GABA do not always conform to the typical scheme of GABA neurons that express GAD, VGAT and GAT (Type I). Indeed, I have found 4 additional types of GABA-positive neurons (Type II to V) that express different combinations of these factors and an extra type (Type VI) that are GABA-negative but express VGAT/unc-47, the sole vesicular transporter of GABA in C. elegans. This atlas is not only essential to understand the function of individual neurons but also to decipher how they modulate the activity of neuronal networks in vivo.

Moreover, I have identified the combinatorial code of transcription factors that specify these different neuronal identities. This has fundamentally redefined our understanding of GABAergic neurotransmission in the worm. This study alongside the ones conducted in cholinergic or glutamatergic neurons has established a framework for the role of transcription factors involved in the final differentiation steps in post-mitotic neurons.

Selected publications

Gendrel M*, Atlas EG, Hobert O*. A cellular and regulatory map of the GABAergic nervous system of C. elegans. Elife. 2016 Oct 14;5:1395. * Corresponding author

 Gendrel M, Rapti G, Richmond JE, Bessereau J-L. A secreted complement-control-related protein ensures acetylcholine receptor clustering. Nature. 2009

Scientific focus :

Marie Gendrel  a fait sa thèse sur la jonction neuro-musculaire, dans l’équipe de Jean-Louis Bessereau.  Elle est actuellement à New York dans l’équipe de Oliver Hobert, travaillant sur les neurones GABAergiques. Elle rentre en France cette année, pour rejoindre l’équipe de Thomas Boulin à Lyon dans un premier temps.