RT Journal Article SR Electronic T1 Deletion of the Presynaptic Scaffold CAST Reduces Active Zone Size in Rod Photoreceptors and Impairs Visual Processing JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 12192 OP 12203 DO 10.1523/JNEUROSCI.0752-12.2012 VO 32 IS 35 A1 Susanne tom Dieck A1 Dana Specht A1 Nicola Strenzke A1 Yamato Hida A1 Vidhyasankar Krishnamoorthy A1 Karl-Friedrich Schmidt A1 Eiji Inoue A1 Hiroyoshi Ishizaki A1 Miki Tanaka-Okamoto A1 Jun Miyoshi A1 Akari Hagiwara A1 Johann H. Brandstätter A1 Siegrid Löwel A1 Tim Gollisch A1 Toshihisa Ohtsuka A1 Tobias Moser YR 2012 UL http://www.jneurosci.org/content/32/35/12192.abstract AB 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 Ca2+ 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 Ca2+ 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.