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

Chattopadhyaya, B., Di Cristo, G., Wu, C. Z., Knott, G., Kuhlman, S. J., Fu, Y., Palmiter, R. D., Huang, Z. J. (2007) GAD67-mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex. Neuron, 54 (6). pp. 889-903. ISSN 0896-6273 (Print)

URL: https://www.ncbi.nlm.nih.gov/pubmed/17582330
DOI: 10.1016/j.neuron.2007.05.015

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.

Item Type: Paper
Uncontrolled 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
Subjects: bioinformatics > genomics and proteomics > small molecules > GABA
bioinformatics > genomics and proteomics > small molecules > GABAergic
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > GAD67
organs, tissues, organelles, cell types and functions > tissues types and functions > visual cortex
CSHL Authors:
Communities: CSHL labs > Huang lab
Depositing User: CSHL Librarian
Date Deposited: 02 Dec 2011 14:33
Last Modified: 10 Jan 2017 15:54
PMCID: PMC2077924
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22983

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