The dendritic patterning of retinal horizontal cells has been shown to be specified by the cone photoreceptor afferents. The present investigation has addressed whether this specification is due to visually dependent synaptic transmission in the outer plexiform layer or to some other early, pre-visual, neural activity. Individually labeled horizontal cells from dark-reared mice, as well as from mice carrying a mutation in the Cacna1f gene, which encodes the pore-forming calcium channel subunit Ca(v)1.4, were assessed for various morphological features. The dark-reared mice showed no alteration in any of these features, despite showing a compromised maximal voltage response in the electroretinograms. The retinas of Cacna1f mutant mice, by contrast, showed conspicuous morphological changes that mimicked the effects observed previously in coneless transgenic mice. These changes were present as early as postnatal day 10, when the shape and density of the cone pedicles appeared normal. Ultrastructurally, however, the pedicles at this early stage, as well as in maturity, lacked synaptic ribbons and the invaginations associated with postsynaptic processes. These results suggest a role for this calcium channel subunit in ribbon assembly in addition to its role in modulating calcium influx and glutamate release. Together, they suggest a complex cascade of interactions between developing cone pedicles and horizontal cell dendrites involving early spontaneous activity, dendritic attraction, ribbon assembly, and pedicle invagination.

The pedicles of cone photoreceptors, labeled with an antibody to mouse cone arrestin (blue), stratify in the outer plexiform layer, where they form synapses with the dendrites of horizontal and bipolar cells. Those synaptic sites are evidenced by the co‐localization of the synaptic ribbon protein, piccolo (red), with the cone arrestin labeling. The remaining red profiles in the outer plexiform layer indicate the sites of the rod spherules. An antibody to cytochrome oxidase (green) labels the mitochondrion‐rich inner segments of all photoreceptors and yields punctate peri‐nuclear labeling within the outer nuclear layer. Many of these features of the outer retina are altered in the Cacna1f‐mutant retina, expressing a defective calcium channel subunit that prevents normal neurotransmission in the outer plexiform layer. J. Comp. Neurol. 506:745–758, 2007. © 2007 Wiley‐Liss, Inc.

The pedicles of cone photoreceptors, labeled with an antibody to mouse cone arrestin (blue), stratify in the outer plexiform layer, where they form synapses with the dendrites of horizontal and bipolar cells. Those synaptic sites are evidenced by the co‐localization of the synaptic ribbon protein, piccolo (red), with the cone arrestin labeling. The remaining red profiles in the outer plexiform layer indicate the sites of the rod spherules. An antibody to cytochrome oxidase (green) labels the mitochondrion‐rich inner segments of all photoreceptors and yields punctate peri‐nuclear labeling within the outer nuclear layer. Many of these features of the outer retina are altered in the Cacna1f‐mutant retina, expressing a defective calcium channel subunit that prevents normal neurotransmission in the outer plexiform layer. J. Comp. Neurol. 506:745–758, 2007. © 2007 Wiley‐Liss, Inc.