title: Nonsynaptic NMDA receptors mediate activity-dependent plasticity of gap junctional coupling in the AII amacrine cell network.
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.
authors.affiliation: Richard S. Ruiz Department of Ophthalmology and Visual Science, University of Texas Medical School, Houston, Texas 77030, USA. Wade.Kothmann@gmail.com
authors.forename: W Wade
authors.initials: WW
authors.lastname: Kothmann
authors.forename: E Brady
authors.initials: EB
authors.lastname: Trexler
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Whitaker
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Massey
authors.forename: John
authors.initials: J
authors.lastname: O'Brien
mesh_terms: D025042:Amacrine Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D017629:Gap Junctions / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D009473:Neuronal Plasticity / Q000502:physiology*; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D011817:Rabbits; D020239:Receptor Cross-Talk / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012160:Retina / Q000187:drug effects / Q000502:physiology; D051245:Retinal Bipolar Cells / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D000097004:Gap Junction delta-2 Protein
chemical_list: D001552:Benzazepines; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017630:Connexins; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D000097004:Gap Junction delta-2 Protein; C534628:SCH 23390; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid