title: Ablation of retinal horizontal cells from adult mice leads to rod degeneration and remodeling in the outer retina.
abstract: In the brain, including the retina, interneurons show an enormous structural and functional diversity. Retinal horizontal cells represent a class of interneurons that form triad synapses with photoreceptors and ON bipolar cells. At this first retinal synapse, horizontal cells modulate signal transmission from photoreceptors to bipolar cells by feedback and feedforward inhibition. To test how the fully developed retina reacts to the specific loss of horizontal cells, these interneurons were specifically ablated from adult mice using the diphtheria toxin (DT)/DT-receptor system and the connexin57 promoter. Following ablation, the retinal network responded with extensive remodeling: rods retracted their axons from the outer plexiform layer and partially degenerated, whereas cones survived. Cone pedicles remained in the outer plexiform layer and preserved synaptic contacts with OFF but not with ON bipolar cells. Consistently, the retinal ON pathway was impaired, leading to reduced amplitudes and prolonged latencies in electroretinograms. However, ganglion cell responses showed only slight changes in time course, presumably because ON bipolar cells formed multiple ectopic synapses with photoreceptors, and visual performance, assessed with an optomotor system, was only mildly affected. Thus, the loss of an entire interneuron class can be largely compensated even by the adult retinal network.
authors.affiliation: Life and Medical Sciences Institute, University of Bonn, D-53115 Bonn, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Sonntag
authors.forename: Karin
authors.initials: K
authors.lastname: Dedek
authors.forename: Birthe
authors.initials: B
authors.lastname: Dorgau
authors.forename: Konrad
authors.initials: K
authors.lastname: Schultz
authors.forename: Karl-Friedrich
authors.initials: KF
authors.lastname: Schmidt
authors.forename: Kerstin
authors.initials: K
authors.lastname: Cimiotti
authors.forename: Reto
authors.initials: R
authors.lastname: Weiler
authors.forename: Siegrid
authors.initials: S
authors.lastname: Löwel
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
authors.forename: Ulrike
authors.initials: U
authors.lastname: Janssen-Bienhold
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D019393:Arrestin / Q000378:metabolism; D017630:Connexins / Q000235:genetics; D015350:Contrast Sensitivity / Q000187:drug effects / Q000235:genetics; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004167:Diphtheria Toxin / Q000633:toxicity; D000076122:Disks Large Homolog 4 Protein; D004596:Electroretinography; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005838:Genotype; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051528:Guanylate Kinases / Q000378:metabolism; D066257:Heparin-binding EGF-like Growth Factor; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D010775:Photic Stimulation; D011042:Poisons / Q000633:toxicity; D051571:Protein Kinase C-alpha / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism / Q000473:pathology; D012162:Retinal Degeneration / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology; D051248:Retinal Horizontal Cells / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D017948:Retinal Rod Photoreceptor Cells / Q000473:pathology* / Q000648:ultrastructure; D013569:Synapses / Q000235:genetics / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors; D014792:Visual Acuity / Q000187:drug effects / Q000235:genetics
chemical_list: D000429:Alcohol Oxidoreductases; D019393:Arrestin; D017630:Connexins; D054815:Cyclic Nucleotide-Gated Cation Channels; D004268:DNA-Binding Proteins; D004167:Diphtheria Toxin; D000076122:Disks Large Homolog 4 Protein; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases; D066257:Heparin-binding EGF-like Growth Factor; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011042:Poisons; D051571:Protein Kinase C-alpha; D018091:Receptors, AMPA; C501447:Dlg4 protein, mouse; C119811:Gja10 protein, mouse; C587884:Hbegf protein, mouse; C485184:enhanced green fluorescent protein; C096794:C-terminal binding protein