Nonsynaptic NMDA receptors mediate activity-dependent plasticity of gap junctional coupling in the AII amacrine cell network

J Neurosci. 2012 May 16;32(20):6747-59. doi: 10.1523/JNEUROSCI.5087-11.2012.

Abstract

Many neurons are coupled by electrical synapses into networks that have emergent properties. In the retina, coupling in these networks is dynamically regulated by changes in background illumination, optimizing signal integration for the visual environment. However, the mechanisms that control this plasticity are poorly understood. We have investigated these mechanisms in the rabbit AII amacrine cell, a multifunctional retinal neuron that forms an electrically coupled network via connexin 36 (Cx36) gap junctions. We find that presynaptic activity of glutamatergic ON bipolar cells drives increased phosphorylation of Cx36, indicative of increased coupling in the AII network. The phosphorylation is dependent on activation of nonsynaptic NMDA receptors that colocalize with Cx36 on AII amacrine cells, and is mediated by CaMKII. This activity-dependent increase in Cx36 phosphorylation works in opposition to dopamine-driven reduction of phosphorylation, establishing a local dynamic regulatory mechanism, and accounting for the nonlinear control of AII coupling by background illumination.

Publication types

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

MeSH terms

  • Amacrine Cells / drug effects
  • Amacrine Cells / metabolism
  • Amacrine Cells / physiology*
  • Animals
  • Benzazepines / pharmacology
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Connexins / metabolism
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Gap Junction delta-2 Protein
  • Gap Junctions / physiology*
  • In Vitro Techniques
  • Male
  • Molecular Imaging / methods
  • Neuronal Plasticity / physiology*
  • Phosphorylation
  • Piperazines / pharmacology
  • Rabbits
  • Receptor Cross-Talk / physiology*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Retina / drug effects
  • Retina / physiology
  • Retinal Bipolar Cells / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*

Substances

  • Benzazepines
  • Connexins
  • Excitatory Amino Acid Antagonists
  • Piperazines
  • Receptors, N-Methyl-D-Aspartate
  • SCH 23390
  • 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2