Age-dependent homeostatic plasticity of GABAergic signaling in developing retinal networks

J Neurosci. 2011 Aug 24;31(34):12159-64. doi: 10.1523/JNEUROSCI.3112-11.2011.

Abstract

Developing retinal ganglion cells fire in correlated spontaneous bursts, resulting in propagating waves with robust spatiotemporal features preserved across development and species. Here we investigate the effects of homeostatic adaptation on the circuits controlling retinal waves. Mouse retinal waves were recorded in vitro for up to 35 h with a multielectrode array in presence of the GABA(A) antagonist bicuculline, allowing us to obtain a precise, time-resolved characterization of homeostatic effects in this preparation. Experiments were performed at P4-P6, when GABA(A) signaling is depolarizing in ganglion cells, and at P7-P10, when GABA(A) signaling is hyperpolarizing. At all ages, bicuculline initially increased the wave sizes and other activity metrics. At P5-P6, wave sizes decreased toward control levels within a few hours while firing remained strong, but this ability to compensate disappeared entirely from P7 onwards. This demonstrates that homeostatic control of spontaneous retinal activity maintains specific network dynamic properties in an age-dependent manner, and suggests that the underlying mechanism is linked to GABA(A) signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Aging / physiology*
  • Animals
  • Animals, Newborn
  • Bicuculline / pharmacology
  • GABA Antagonists / pharmacology
  • Homeostasis / drug effects
  • Homeostasis / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways / physiology
  • Neuronal Plasticity / physiology*
  • Receptors, GABA-A / physiology
  • Retina / cytology
  • Retina / growth & development*
  • Retina / physiology*
  • Retinal Ganglion Cells / cytology
  • Retinal Ganglion Cells / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • gamma-Aminobutyric Acid / physiology*

Substances

  • GABA Antagonists
  • Receptors, GABA-A
  • gamma-Aminobutyric Acid
  • Bicuculline