Non-cell-autonomous factor induces the transition from excitatory to inhibitory GABA signaling in retina independent of activity

Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22302-7. doi: 10.1073/pnas.1008775108. Epub 2010 Dec 6.


During development, the effect of activating GABA(A) receptors switches from depolarizing to hyperpolarizing. Several environmental factors have been implicated in the timing of this GABA switch, including neural activity, although these observations remain controversial. By using acutely isolated retinas from KO mice and pharmacological manipulations in retinal explants, we demonstrate that the timing of the GABA switch in retinal ganglion cells (RGCs) is unaffected by blockade of specific neurotransmitter receptors or global activity. In contrast to RGCs in the intact retina, purified RGCs remain depolarized by GABA, indicating that the GABA switch is not cell-autonomous. Indeed, purified RGCs cocultured with dissociated cells from the superior colliculus or cultured in media conditioned by superior collicular cells undergo a normal switch. Thus, a diffusible signal that acts independent of local circuit activity regulates the maturation of GABAergic inhibition in mouse RGCs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cells, Cultured
  • Coculture Techniques
  • GABA-A Receptor Agonists / pharmacology
  • Mice
  • Mice, Knockout
  • Muscimol / pharmacology
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Superior Colliculi / cytology
  • Superior Colliculi / metabolism
  • gamma-Aminobutyric Acid / metabolism*


  • GABA-A Receptor Agonists
  • Muscimol
  • gamma-Aminobutyric Acid