title: Deletion of the presynaptic scaffold CAST reduces active zone size in rod photoreceptors and impairs visual processing.
abstract: How size and shape of presynaptic active zones are regulated at the molecular level has remained elusive. Here we provide insight from studying rod photoreceptor ribbon-type active zones after disruption of CAST/ERC2, one of the cytomatrix of the active zone (CAZ) proteins. Rod photoreceptors were present in normal numbers, and the a-wave of the electroretinogram (ERG)--reflecting their physiological population response--was unchanged in CAST knock-out (CAST(-/-)) mice. Using immunofluorescence and electron microscopy, we found that the size of the rod presynaptic active zones, their Ca(2+) channel complement, and the extension of the outer plexiform layer were diminished. Moreover, we observed sprouting of horizontal and bipolar cells toward the outer nuclear layer indicating impaired rod transmitter release. However, rod synapses of CAST(-/-) mice, unlike in mouse mutants for the CAZ protein Bassoon, displayed anchored ribbons, normal vesicle densities, clustered Ca(2+) channels, and essentially normal molecular organization. The reduction of the rod active zone size went along with diminished amplitudes of the b-wave in scotopic ERGs. Assuming, based on the otherwise intact synaptic structure, an unaltered function of the remaining release apparatus, we take our finding to suggest a scaling of release rate with the size of the active zone. Multielectrode-array recordings of retinal ganglion cells showed decreased contrast sensitivity. This was also observed by optometry, which, moreover, revealed reduced visual acuity. We conclude that CAST supports large active zone size and high rates of transmission at rod ribbon synapses, which are required for normal vision.
authors.affiliation: Department of Synaptic Plasticity, Max Planck Institute for Brain Research, D-60528 Frankfurt/Main, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: tom Dieck
authors.forename: Dana
authors.initials: D
authors.lastname: Specht
authors.forename: Nicola
authors.initials: N
authors.lastname: Strenzke
authors.forename: Yamato
authors.initials: Y
authors.lastname: Hida
authors.forename: Vidhyasankar
authors.initials: V
authors.lastname: Krishnamoorthy
authors.forename: Karl-Friedrich
authors.initials: KF
authors.lastname: Schmidt
authors.forename: Eiji
authors.initials: E
authors.lastname: Inoue
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ishizaki
authors.forename: Miki
authors.initials: M
authors.lastname: Tanaka-Okamoto
authors.forename: Jun
authors.initials: J
authors.lastname: Miyoshi
authors.forename: Akari
authors.initials: A
authors.lastname: Hagiwara
authors.forename: Johann H
authors.initials: JH
authors.lastname: Brandstätter
authors.forename: Siegrid
authors.initials: S
authors.lastname: Löwel
authors.forename: Tim
authors.initials: T
authors.lastname: Gollisch
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ohtsuka
authors.forename: Tobias
authors.initials: T
authors.lastname: Moser
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002678:Chimera; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010775:Photic Stimulation / Q000379:methods; D017729:Presynaptic Terminals / Q000378:metabolism*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology; D014796:Visual Perception / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; C505599:Erc2 protein, mouse