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

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State: Serval
Version: author
Serval ID
serval:BIB_9B100739FF7B
Type
Article: article from journal or magazin.
Collection
Publications
Title
GAD67-mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex
Journal
Neuron
Author(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)
Publication state
Published
Issued date
06/2007
Peer-reviewed
Oui
Volume
54
Number
6
Pages
889-903
Language
english
Notes
In Vitro
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't --- Old month value: Jun 21
Abstract
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.
Keywords
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
Yes
Create date
24/01/2008 15:26
Last modification date
08/05/2019 22:36
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