Differential modulation of retinal ganglion cell light responses by orthosteric and allosteric metabotropic glutamate receptor 8 compounds
| Autor: | Robert M. Duvoisin, Catherine W. Morgans, Brian T. Reed |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Retinal Ganglion Cells
Allosteric modulator Glycine Receptors Metabotropic Glutamate Retinal ganglion Benzoates Article Cellular and Molecular Neuroscience Mice Organ Culture Techniques Allosteric Regulation medicine Animals DCPG Pharmacology Metabotropic glutamate receptor 8 Retina Chemistry Glutamate receptor Mice Inbred C57BL medicine.anatomical_structure Retinal ganglion cell Metabotropic glutamate receptor Thioglycolates Biophysics Acetanilides sense organs Neuroscience Photic Stimulation |
| Zdroj: | Neuropharmacology. 67 |
| ISSN: | 1873-7064 |
| Popis: | To investigate the role of mGluR8 in modulating the synaptic responses of retinal ganglion cells, we used a recently identified positive allosteric modulator of mGluR8, AZ12216052 (AZ) and the mGluR8-specific orthosteric agonist (S)-3,4-dicarboxyphenylglycine (DCPG). These agents were applied to whole-cell voltage-clamped ganglion cells from an isolated, superfused mouse retina preparation. DCPG reduced OFF-ganglion cell excitatory currents, whereas AZ enhanced the peak excitatory currents in ON-, OFF-, and ON–OFF-ganglion cells. The effects on ganglion cell inhibitory currents were more varied. The effects of the allosteric modulator were stronger for bright stimuli than for dim stimuli, consistent with receptor stimulation by endogenous glutamate being stronger during bright light stimulation and with mGluR8 receptors mainly being localized away from glutamate release sites, immuno-labeled with VGLUT1. The differential sensitivity of ganglion cell light responses to DCPG and AZ supports multiple sites where mGluR8 modulates the light responses of ganglion cells. |
| Databáze: | OpenAIRE |
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