Early depolarizing GABA controls critical-period plasticity in the rat visual cortex

Nat Neurosci. 2015 Jan;18(1):87-96. doi: 10.1038/nn.3890. Epub 2014 Dec 8.


Hyperpolarizing and inhibitory GABA regulates critical periods for plasticity in sensory cortices. Here we examine the role of early, depolarizing GABA in the control of plasticity mechanisms. We report that brief interference with depolarizing GABA during early development prolonged critical-period plasticity in visual cortical circuits without affecting the overall development of the visual system. The effects on plasticity were accompanied by dampened inhibitory neurotransmission, downregulation of brain-derived neurotrophic factor (BDNF) expression and reduced density of extracellular matrix perineuronal nets. Early interference with depolarizing GABA decreased perinatal BDNF signaling, and a pharmacological increase of BDNF signaling during GABA interference rescued the effects on plasticity and its regulators later in life. We conclude that depolarizing GABA exerts a long-lasting, selective modulation of plasticity of cortical circuits by a strong crosstalk with BDNF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Bumetanide / pharmacology
  • Contrast Sensitivity / drug effects
  • Contrast Sensitivity / physiology
  • Critical Period, Psychological*
  • Diuretics / pharmacology
  • Evoked Potentials, Visual / drug effects
  • Evoked Potentials, Visual / physiology
  • Female
  • GABA Antagonists / pharmacology
  • Male
  • Maze Learning
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Rats
  • Rats, Long-Evans
  • Visual Cortex / drug effects
  • Visual Cortex / growth & development
  • Visual Cortex / physiology*
  • gamma-Aminobutyric Acid / physiology*


  • Diuretics
  • GABA Antagonists
  • Bumetanide
  • gamma-Aminobutyric Acid