Early changes in synaptic connectivity following progressive photoreceptor degeneration in RCS rats

Please use this identifier to cite or link to this item: http://hdl.handle.net/10045/16761
Información del item - Informació de l'item - Item information
Title: Early changes in synaptic connectivity following progressive photoreceptor degeneration in RCS rats
Authors: Cuenca, Nicolás | Pinilla Lozano, Isabel | Sauvé, Yves | Lund, Raymond D.
Research Group/s: Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS)
Center, Department or Service: Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología
Keywords: Bipolar | Horizontal | Outer plexiform layer | Photoreceptor | Retinal degeneration
Knowledge Area: Oftalmología | Fisiología
Issue Date: 16-Sep-2005
Publisher: Blackwell Publishing | Federation of European Neuroscience Societies
Citation: CUENCA NAVARRO, Nicolás, et al. "Early changes in synaptic connectivity following progressive photoreceptor degeneration in RCS rats". European Journal of Neuroscience. Vol. 22, No. 5 (Sept. 2005). ISSN 0953-816X, pp. 1057-1072
Abstract: The Royal College of Surgeons (RCS) rat has a retinal pigment epithelial cell defect that causes progressive loss of photoreceptors. Although it is extensively used in retinal degeneration and repair studies, how photoreceptor degeneration affects retinal circuitry has not been fully explored. This study examined the changes in synaptic connectivity between photoreceptors and their target cells using immunocytochemistry and correlated these changes with retinal function using the electroretinogram (ERG). Immunostaining with bassoon and synaptophysin (as presynaptic markers) and metabotropic glutamate receptor (mGluR6, a postsynaptic marker for ON-bipolar dendrites) was already impaired at postnatal day (P) 21 and progressively lost with infrequent pairing of presynaptic and postsynaptic elements at P60. By P90 to P120, staining became increasingly patchy and was eventually restricted to sparsely and irregularly distributed foci in which the normal pairing of presynaptic and postsynaptic markers was lost. ERG results showed that mixed scotopic a-waves and b-waves were already reduced by P21 but not oscillatory potentials. While cone-driven responses (photopic b-wave) reached normal levels at P30, they were impaired by P60 but could still be recorded at P120, although with reduced amplitude; rod responses never reached normal amplitudes. Thus, only cone-driven activity attained normal levels, but declined rapidly thereafter. In conclusion, the synaptic markers associated with photoreceptors and processes of bipolar and horizontal cells show abnormalities prior to significant photoreceptor loss. These changes are paralleled with the deterioration of specific aspects of ERG responsiveness with age. Besides providing information on the effects of photoreceptor dysfunction and loss on connection patterns in the retina, the work addresses the more general issue of how disorder of input neurons affects downstream circuitry.
Sponsor: This work was supported by grants from Foundation Fighting Blindness, NIH (EY14038), Wynn Foundation, Research to Prevent Blindness, Johnson and Johnson Focused Giving Program, and a joint equipment grant from the University of Utah. Dr I Pinilla was supported by a grant from the Spanish Government (FIS 02⁄5010, BA 03⁄0016).
URI: http://hdl.handle.net/10045/16761
ISSN: 0953-816X (Print) | 1460-9568 (Online)
DOI: 10.1111/j.1460-9568.2005.04300.x
Language: eng
Type: info:eu-repo/semantics/article
Rights: The definitive version is available at www.blackwell-synergy.com
Peer Review: si
Publisher version: http://dx.doi.org/10.1111/j.1460-9568.2005.04300.x
Appears in Collections:INV - NEUROVIS - Artículos de Revistas

Files in This Item:
Files in This Item:
File Description SizeFormat 
ThumbnailEarly_changes_synaptic.pdfVersión final (acceso restringido)3,31 MBAdobe PDFOpen    Request a copy

Items in RUA are protected by copyright, with all rights reserved, unless otherwise indicated.