GAD67-mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex

Détails

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_9B100739FF7B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
GAD67-mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex
Périodique
Neuron
Auteur(s)
Chattopadhyaya B., Di Cristo G., Wu C. Z., Knott G., Kuhlman S., Fu Y., Palmiter R. D., Huang Z. J.
ISSN
0896-6273 (Print)
Statut éditorial
Publié
Date de publication
06/2007
Peer-reviewed
Oui
Volume
54
Numéro
6
Pages
889-903
Langue
anglais
Notes
In Vitro
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Jun 21
Résumé
The development of GABAergic inhibitory circuits is shaped by neural activity, but the underlying mechanisms are unclear. Here, we demonstrate a novel function of GABA in regulating GABAergic innervation in the adolescent brain, when GABA is mainly known as an inhibitory transmitter. Conditional knockdown of the rate-limiting synthetic enzyme GAD67 in basket interneurons in adolescent visual cortex resulted in cell autonomous deficits in axon branching, perisomatic synapse formation around pyramidal neurons, and complexity of the innervation fields; the same manipulation had little influence on the subsequent maintenance of perisomatic synapses. These effects of GABA deficiency were rescued by suppressing GABA reuptake and by GABA receptor agonists. Germline knockdown of GAD67 but not GAD65 showed similar deficits, suggesting a specific role of GAD67 in the maturation of perisomatic innervation. Since intracellular GABA levels are modulated by neuronal activity, our results implicate GAD67-mediated GABA synthesis in activity-dependent regulation of inhibitory innervation patterns.
Mots-clé
Animals Axons/physiology Glutamate Decarboxylase/genetics/*physiology Green Fluorescent Proteins/metabolism Isoenzymes/genetics/*physiology Mice Mice, Transgenic Neural Inhibition/*physiology Neurons/classification/cytology/physiology Organ Culture Techniques Parvalbumins/metabolism Phosphopyruvate Hydratase/metabolism Signal Transduction/*physiology Synapses/*physiology Time Factors Transfection/methods Visual Cortex/*cytology/metabolism Visual Pathways/cytology/physiology gamma-Aminobutyric Acid/*metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 15:26
Dernière modification de la notice
08/05/2019 22:36
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