An Allosteric Regulator of R7-RGS Proteins Influences Light-Evoked Activity and Glutamatergic Waves in the Inner Retina
| Autor: | Bradly Q. Vo, Alexander V. Kolesnikov, Vladimir J. Kefalov, Susan M. Culican, Kendall J. Blumer, Matthew D. Cain, Daniel Kerschensteiner |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Retinal Ganglion Cells
Retinal Bipolar Cells Allosteric modulator Light genetic structures Visual Acuity Action Potentials lcsh:Medicine Neurotransmission Biology Retinal ganglion Retina Choline Contrast Sensitivity Mice 03 medical and health sciences Glutamatergic 0302 clinical medicine Allosteric Regulation Glutamates Retinal Rod Photoreceptor Cells medicine Animals lcsh:Science 030304 developmental biology Transcription Factor Brn-3A 0303 health sciences Multidisciplinary medicine.diagnostic_test lcsh:R Anatomy eye diseases Cell biology Mice Inbred C57BL Amacrine Cells medicine.anatomical_structure Animals Newborn Retinal Cone Photoreceptor Cells lcsh:Q sense organs Gene Deletion RGS Proteins 030217 neurology & neurosurgery Research Article Visual phototransduction Electroretinography |
| Zdroj: | PLoS ONE, Vol 8, Iss 12, p e82276 (2013) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0082276 |
| Popis: | In the outer retina, G protein-coupled receptor (GPCR) signaling mediates phototransduction and synaptic transmission between photoreceptors and ON bipolar cells. In contrast, the functions of modulatory GPCR signaling networks in the inner retina are less well understood. We addressed this question by determining the consequences of augmenting modulatory Gi/o signaling driven by endogenous transmitters. This was done by analyzing the effects of genetically ablating the R7 RGS-binding protein (R7BP), a membrane-targeting protein and positive allosteric modulator of R7-RGS (regulator of the G protein signaling 7) family that deactivates Gi/oα subunits. We found that R7BP is expressed highly in starburst amacrine cells and retinal ganglion cells (RGCs). As indicated by electroretinography and multielectrode array recordings of adult retina, ablation of R7BP preserved outer retina function, but altered the firing rate and latency of ON RGCs driven by rods and cones but not rods alone. In developing retina, R7BP ablation increased the burst duration of glutamatergic waves whereas cholinergic waves were unaffected. This effect on glutamatergic waves did not result in impaired segregation of RGC projections to eye-specific domains of the dorsal lateral geniculate nucleus. R7BP knockout mice exhibited normal spatial contrast sensitivity and visual acuity as assessed by optomotor reflexes. Taken together these findings indicate that R7BP-dependent regulation of R7-RGS proteins shapes specific aspects of light-evoked and spontaneous activity of RGCs in mature and developing retina. |
| Databáze: | OpenAIRE |
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