title: Afferents and homotypic neighbors regulate horizontal cell morphology, connectivity, and retinal coverage.
abstract: Horizontal cells are inhibitory interneurons with laterally oriented dendrites that overlap one another, contacting the pedicles of cone photoreceptors. Because of their regular spacing, the network of horizontal cells provides a uniform coverage of the retinal surface. The developmental processes establishing these network properties are undefined, but cell-intrinsic instructions and interactions with other cells have each been suggested to play a role. Here, we show that the intercellular spacing of horizontal cells is essentially independent of genetic background and is predicted by local density, suggesting that horizontal cell positioning is modulated by proximity to other horizontal cells. Dendritic field area compensates for this variation in intercellular spacing, maintaining constant dendritic coverage between strains. Functional dendritic overlap is achieved anatomically at the level of the pedicles, where horizontal cells interact with one another to establish their connectivity: the number of dendritic terminals contacting a pedicle changes, reciprocally, between neighboring horizontal cells during development based on their relative proximity to each pedicle. Cellular morphology is also shown to be regulated by the afferents themselves: afferent elimination before innervation does not alter dendritic field size nor stratification but compromises dendritic branching and prevents terminal formation. Afferent and homotypic interactions therefore generate the morphology, spacing, and connectivity of horizontal cells underlying their functional coverage of the retina.
authors.affiliation: Neuroscience Research Institute and Department of Psychology, University of California at Santa Barbara, Santa Barbara, California 93106-5060, USA. breese@psych.ucsb.edu
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Reese
authors.forename: Mary A
authors.initials: MA
authors.lastname: Raven
authors.forename: Stephanie B
authors.initials: SB
authors.lastname: Stagg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count / Q000379:methods; D048429:Cell Size; D003712:Dendrites / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014442:Monophenol Monooxygenase / Q000235:genetics; D009475:Neurons, Afferent / Q000502:physiology*; D012160:Retina / Q000166:cytology*; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology; D051248:Retinal Horizontal Cells / Q000166:cytology* / Q000502:physiology*; D013045:Species Specificity; D014795:Visual Pathways / Q000033:anatomy & histology*
chemical_list: D014442:Monophenol Monooxygenase
references.citation: Eur J Neurosci. 1999 Aug;11(8):2965-78
references.pmid: 10457191
references.citation: J Neurosci. 1999 Oct 15;19(20):8919-30
references.pmid: 10516311
references.citation: Nat Genet. 1999 Dec;23(4):466-70
references.pmid: 10581037
references.citation: Trends Neurosci. 2000 Jan;23(1):26-34
references.pmid: 10631786
references.citation: Eur J Neurosci. 2000 Feb;12(2):613-20
references.pmid: 10712641
references.citation: Brain Res Brain Res Rev. 2000 Apr;32(1):146-58
references.pmid: 10751664
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11020-5
references.pmid: 10995468
references.citation: Nat Neurosci. 2000 Nov;3(11):1121-7
references.pmid: 11036269
references.citation: Curr Opin Neurobiol. 2001 Feb;11(1):118-26
references.pmid: 11179881
references.citation: Nat Neurosci. 2001 Apr;4(4):359-65
references.pmid: 11276225
references.citation: Prog Retin Eye Res. 2002 Mar;21(2):153-68
references.pmid: 12062533
references.citation: Eur J Neurosci. 1989 Sep;1(5):421-435
references.pmid: 12106129
references.citation: J Neurosci. 2002 Sep 1;22(17):7639-49
references.pmid: 12196587
references.citation: Nat Rev Neurosci. 2002 Oct;3(10):803-12
references.pmid: 12360324
references.citation: J Comp Neurol. 2002 Dec 9;454(2):168-76
references.pmid: 12412141
references.citation: Cell. 2003 Jan 24;112(2):157-67
references.pmid: 12553905
references.citation: Mol Vis. 2003 Feb 15;9:31-42
references.pmid: 12592228
references.citation: Invest Ophthalmol Vis Sci. 2003 Mar;44(3):965-73
references.pmid: 12601016
references.citation: Curr Biol. 2003 Apr 15;13(8):618-26
references.pmid: 12699617
references.citation: J Comp Neurol. 2003 Jun 16;461(1):123-36
references.pmid: 12722109
references.citation: Nat Neurosci. 2003 Nov;6(11):1169-77
references.pmid: 14528308
references.citation: Neuron. 2003 Oct 9;40(2):229-42
references.pmid: 14556706
references.citation: J Comp Neurol. 2004 Mar 22;471(1):11-25
references.pmid: 14983472
references.citation: Nat Neurosci. 2004 Apr;7(4):327-32
references.pmid: 15048120
references.citation: Vis Neurosci. 2004 Jan-Feb;21(1):13-22
references.pmid: 15137578
references.citation: Neuron. 1992 Sep;9(3):429-40
references.pmid: 1524826
references.citation: Neuroscience. 2004;127(2):301-17
references.pmid: 15262321
references.citation: Neuron. 2004 Aug 19;43(4):475-85
references.pmid: 15312647
references.citation: J Comp Neurol. 1992 Jul 1;321(1):46-64
references.pmid: 1613139
references.citation: Vis Neurosci. 1991 Feb;6(2):95-111
references.pmid: 2049333
references.citation: Science. 1987 May 15;236(4803):848-51
references.pmid: 3576202
references.citation: J Comp Neurol. 1974 Jul 1;156(1):81-93
references.pmid: 4836656
references.citation: Invest Ophthalmol. 1968 Jun;7(3):250-68
references.pmid: 5655873
references.citation: Proc R Soc Lond B Biol Sci. 1981 May 22;212(1187):157-75
references.pmid: 6166012
references.citation: J Comp Neurol. 1984 Nov 1;229(3):362-73
references.pmid: 6501608
references.citation: Nature. 1982 Jun 24;297(5868):683-5
references.pmid: 7088156
references.citation: J Comp Neurol. 1995 Apr 10;354(3):438-58
references.pmid: 7608331
references.citation: Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):4002-5
references.pmid: 7732021
references.citation: J Comp Neurol. 1994 May 15;343(3):387-405
references.pmid: 8027449
references.citation: J Comp Neurol. 1994 May 15;343(3):406-27
references.pmid: 8027450
references.citation: Vis Neurosci. 1994 May-Jun;11(3):501-17
references.pmid: 8038125
references.citation: J Neurosci. 1996 May 15;16(10):3381-96
references.pmid: 8627374
references.citation: J Comp Neurol. 1997 Nov 10;388(1):47-63
references.pmid: 9364238
references.citation: Semin Cell Dev Biol. 1998 Jun;9(3):249-55
references.pmid: 9665859
references.citation: Neuron. 1998 Sep;21(3):481-93
references.pmid: 9768836