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B. E. Reese, M. A. Raven, N. C. Orton, H. Nassar, G. A. Williams, W. K. Stell, G. H. Jacobs, N. T. Bech-Hansen; Afferent Control of Horizontal Cell Morphology: Dissecting the Roles of Pedicle Formation and Visual Activity. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5697.
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© ARVO (1962-2015); The Authors (2016-present)
The horizontal cells of the retina require innervation from the cone photoreceptors in order to establish their normal dendritic morphology, evidenced in studies using coneless transgenic mice. The present study has examined the relative roles of pedicle formation and visual activity in this process.
EM, immuno- and DiI-labeling techniques were used to examine the morphology of cones and horizontal cells (1) in dark-reared mice, in which all light-modulated retinal activity is prevented, and (2) in Cacna1f-mutant mice, in which all photoreceptor neurotransmission in the OPL is disrupted.
Horizontal cell number, morphology and pedicle innervation were all unchanged in dark-reared mice, despite a significant reduction in the amplitude of the cone-driven signal as evidenced by ERG V-log I functions. In adult Cacna1f-mutant mice, horizontal cells showed an atrophic dendritic arbor containing few terminal clusters, similar to the phenotype in coneless transgenic mice. At P10, horizontal cells in the Cacna1f-mutant retinas showed hypertrophic dendritic branching without terminal clustering, also similar to that found in coneless transgenic mice at this age. In the adult Cacna1f-mutant retina, immunolabeled cone pedicles were frequently degenerate and had retracted from the OPL; at P10, however, cone pedicles had a normal morphology, stratifying within the OPL, whereas they failed to differentiate in the coneless transgenic retina. Ultrastructurally, pedicles in the Cacna1f-mutant retina at P10 failed to show ribbon synapses and the invaginations typically associated with them; rather, the postsynaptic processes were subjacent to the basal surface of the pedicle in the OPL.
Disruption of calcium levels or channel protein structure in the Cacna1f-mutant retina prevents the development of normal synaptic relationships between pedicles and horizontal cell dendrites. Because the morphological changes observed must be independent of any role associated with visually modulated activity, and because they occur whether or not cone pedicles are present, these results suggest that early interactions at the cone-horizontal cell synapse set in motion a cascade of events leading to dendritic branch stabilization and terminal cluster formation.
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