Activity-dependent regulation of inhibitory synapse development by Npas4

Nature. 2008 Oct 30;455(7217):1198-204. doi: 10.1038/nature07319. Epub 2008 Sep 24.

Abstract

Neuronal activity regulates the development and maturation of excitatory and inhibitory synapses in the mammalian brain. Several recent studies have identified signalling networks within neurons that control excitatory synapse development. However, less is known about the molecular mechanisms that regulate the activity-dependent development of GABA (gamma-aminobutyric acid)-releasing inhibitory synapses. Here we report the identification of a transcription factor, Npas4, that plays a role in the development of inhibitory synapses by regulating the expression of activity-dependent genes, which in turn control the number of GABA-releasing synapses that form on excitatory neurons. These findings demonstrate that the activity-dependent gene program regulates inhibitory synapse development, and suggest a new role for this program in controlling the homeostatic balance between synaptic excitation and inhibition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cells, Cultured
  • Electrophysiology
  • Gene Expression Regulation
  • Hippocampus / cytology
  • Mice
  • Neurons / metabolism
  • Rats
  • Synapses / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transfection
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Brain-Derived Neurotrophic Factor
  • Npas4 protein, mouse
  • Transcription Factors
  • gamma-Aminobutyric Acid

Associated data

  • GEO/GSE11256
  • GEO/GSE11258