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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Chattopadhyaya, B; Di Cristo, G; Wu, CZ; Knott, G; Kuhlman, S; Fu, Y; Palmiter, RD; Huang, ZJ

Published Date

  • June 21, 2007

Published In

Volume / Issue

  • 54 / 6

Start / End Page

  • 889 - 903

PubMed ID

  • 17582330

Pubmed Central ID

  • PMC2077924

International Standard Serial Number (ISSN)

  • 0896-6273

Digital Object Identifier (DOI)

  • 10.1016/j.neuron.2007.05.015

Language

  • eng

Conference Location

  • United States