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P. Bayley, L. Akileswaran, W.R. Taylor, C.W. Morgans; Differential Effect on Rod and Cone Ribbon Synapses of the Cav1.4 Calcium Channel Mutation in the Nob2 Mouse . Invest. Ophthalmol. Vis. Sci. 2006;47(13):2851.
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© ARVO (1962-2015); The Authors (2016-present)
The retinal disease Incomplete Congenital Stationary Night Blindness (CSNB2) is characterized by a reduction in neurotransmission between photoreceptors and bipolar cells. The gene responsible for CSNB2 is CACNA1F, which encodes the L–type calcium channel, Cav1.4. In the mammalian retina, Cav1.4 is found at rod and cone ribbon synapses. Here we investigate ribbon synapse structure and function in the nob2 mouse, which contains a naturally occurring null mutation in the cacna1f gene.
Retinal sections were labeled by immunofluorescence according to standard procedures (Berntson and Morgans, 2003) and imaged using a Zeiss LSM510 confocal microscope. For ultrastructural analysis, retinas were prepared for transmission electron microscopy using standard procedures (Bramblett et al., 2004), and viewed on a FEI Tecnai 12 microscope. Light–evoked currents were recorded from bipolar cells in the mouse retinal slice preparation (Berntson and Taylor, 2003).
Rod terminals are much more severely affected than cone terminals in the nob2 retina. In addition to the absence of Cav1.4 immunostaining, the majority of ribbon synapse–associated markers are severely reduced or missing from the nob2 outer plexiform layer. Rod synapses are reduced in number, and are frequently seen in ectopic locations in the nob2 outer nuclear layer. Ultrastructural analysis of nob2 rod terminals reveals a dramatic reduction in synaptic ribbon number and an abnormal morphology of the remaining ribbons. Furthermore, invasion of the rod spherule by postsynaptic rod bipolar cell and horizontal cell processes is greatly reduced in nob2, leading to the loss of the characteristic invaginating synapse morphology. In contrast, the anatomy of cone ribbon synapses appears largely intact. Electrophysiological recordings from the nob2 retina reveal that light responses are undetectable in rod bipolar cells, but that light responses can be recorded in cone bipolar cells, indicating that neurotransmission still occurs at the nob2 cone pedicle. The relative preservation of cone function and morphology may be attributable to the expression of additional L–type calcium channels, for example Cav1.3, by cone photoreceptors.
The anatomical characterization of the nob2 retina provides evidence that the Cav1.4 calcium channel is required for the proper ultrastructure and functioning of the rod ribbon synapse. Study of this mouse will provide insight into the visual defects associated with CSNB2, as well as into the normal development and function of the rod ribbon synapse.
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