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Felice Dunn, Anthony Azevedo, Rachel Wong; Development of the cone photoreceptor-to-cone bipolar cell synapse depends on visual activity. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2500.
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© ARVO (1962-2015); The Authors (2016-present)
Prior work has demonstrated a role for visual experience in the development of the inner retina (Tian & Copenhagen 2001, Neuron 32:439-49), as well as in central visual pathways (Yoshii et al. 2003, PNAS 100:1334-39; Lu & Constantine-Paton 2004, Neuron 43:237-49). At the cone-to-cone bipolar cell synapse, different bipolar cells establish their mature connectivity patterns with cone photoreceptors either before or after eye opening, depending on the cell type (Dunn & Wong 2012, J Neurosci 32:10306-17). Therefore, we wondered whether visual activity plays a differential role in establishing the cone-to-cone bipolar cell synapse across bipolar cell types.
We used the Grm6-tdTomato mouse line, in which a sparse population of ON bipolar cells expresses tdTomato under the mGluR6 promoter. We focused on the types 6, 7, and 8 ON cone bipolar cells described previously (Wässle et al. 2009, J Neurosci 29:106-17). Mice were either normally reared in a 12 hr light-dark cycle or in complete darkness. Antibodies against cone arrestin (Cheryl Craft, USC) and mGluR6 (Catherine Morgans, OHSU) were used to label presynaptic cones and postsynaptic glutamate receptors. We analyzed confocal images of the synaptic structure of each bipolar cell type in three-dimensions. Functional measures of the cone-to-cone bipolar cell synapse were made using electroretinograms (ERG) of in vitro retina. Pharmacology was used to isolate specific glutamate receptor contributions to the waveform.
We found that dark-rearing has a differential effect on the development of cone contacts by the types 6, 7, and 8 ON cone bipolar cells. The early-developing type 6 cone bipolar cells contacted the same number of cones in dark-reared mice as in normally-reared mice. The establishment, maintenance and pruning of cone contacts by the late-developing type 8 cone bipolar cells were disrupted by dark-rearing. Across all three bipolar cell types, glutamate receptor allocation to dendritic terminals decreased significantly in dark-reared mice. ERGs reveal that while the rod-driven a- and b-waves were within the range of normally-reared animals, the cone-driven b-waves decreased in dark-reared mice.
Our results suggest that the development of cone-to-cone bipolar cell contacts, glutamate receptor allocation, and establishing proper function of the visual system’s first synapse require visual activity.
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