title: Rod bipolar cells and horizontal cells form displaced synaptic contacts with rods in the outer nuclear layer of the nob2 retina.
abstract: The nob2 mouse carries a null mutation in the Cacna1f gene, which encodes the pore-forming subunit of the L-type calcium channel, Ca(v)1.4. The loss of the electroretinogram b-wave in these mice suggests a severe reduction in transmission between photoreceptors and second-order neurons in the retina and supports a central role for the Ca(v)1.4 calcium channel at photoreceptor ribbon synapses, to which it has been localized. Here we show that the loss of Ca(v)1.4 leads to the aberrant outgrowth of rod bipolar cell dendrites and horizontal cell processes into the outer nuclear layer (ONL) of the nob2 retina and to the formation of ectopic synaptic contacts with rod photoreceptors in the ONL. Ectopic contacts are predominantly between rods and rod bipolar cells, with horizontal cell processes also present at some sites. Ectopic contacts contain apposed pre- and postsynaptic specializations, albeit with malformed synaptic ribbons. Cone photoreceptor terminals do not participate in ectopic contacts in the ONL. During retinal development, ectopic contacts appear in the days after eye opening, appearing progressively farther into the ONL at later postnatal stages. Ectopic contacts develop at the tips of rod bipolar cell dendrites and are less frequently associated with the tips of horizontal cell processes, consistent with the adult phenotype. The relative occurrence of pre- and postsynaptic markers in the ONL during development suggests a mechanism for the formation of ectopic synaptic contacts that is driven by the retraction of rod photoreceptor terminals and neurite outgrowth by rod bipolar cell dendrites.
authors.affiliation: Neurological Sciences Institute, Oregon Health and Science University, West Campus, Beaverton, Oregon 97006, USA.
authors.forename: Philippa R
authors.initials: PR
authors.lastname: Bayley
authors.forename: Catherine W
authors.initials: CW
authors.lastname: Morgans
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics*; D020746:Calcium Channels, L-Type; D002454:Cell Differentiation / Q000235:genetics; D002828:Choristoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D016189:Dystrophin / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation / Q000235:genetics; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D051245:Retinal Bipolar Cells / Q000378:metabolism / Q000648:ultrastructure*; D051248:Retinal Horizontal Cells / Q000378:metabolism / Q000648:ultrastructure*; D017948:Retinal Rod Photoreceptor Cells / Q000002:abnormalities* / Q000378:metabolism / Q000648:ultrastructure*; D013570:Synaptic Membranes / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics; D014785:Vision, Ocular / Q000235:genetics
chemical_list: D015415:Biomarkers; C480684:Cacna1f protein, mouse; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D016189:Dystrophin; D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6