Thenob2mouse, a null mutation inCacna1f: Anatomical and functional abnormalities in the outer retina and their consequences on ganglion cell visual responses

Autor: Akihiro Ikeda, Kirstan A. Vessey, Ronald E. Hurd, Britt A. Johnson, Neal S. Peachey, S. Nusinowitz, Catherine W. Morgans, Bo Chang, John R. Heckenlively, Nicholas C. Brecha, Ronald G. Gregg, Maureen A. McCall, Muriel T. Davisson, Philippa R. Bayley, Arlene A. Hirano, Dennis S. Rice, Norm L. Hawes
Rok vydání: 2006
Předmět:
Retinal Ganglion Cells
Calbindins
Time Factors
genetic structures
Calcium Channels
L-Type
Physiology
Action Potentials
Outer plexiform layer
Dark Adaptation
Biology
Visual system
Receptors
Metabotropic Glutamate
Retinal ganglion
Article
Retina
Mice
Peanut Agglutinin
S100 Calcium Binding Protein G
Electroretinography
Reaction Time
medicine
Animals
Visual Pathways
RNA
Messenger
Outer nuclear layer
Protein Kinase C
Voltage-dependent calcium channel
medicine.diagnostic_test
Reverse Transcriptase Polymerase Chain Reaction
Age Factors
Dose-Response Relationship
Radiation
Receptors
Neurokinin-3
Photoreceptor ribbon synapse
Phosphoproteins
Immunohistochemistry
Mice
Mutant Strains
Sensory Systems
DNA-Binding Proteins
Alcohol Oxidoreductases
medicine.anatomical_structure
Mutation
Synapses
Calcium Channels
sense organs
Co-Repressor Proteins
Neuroscience
Photic Stimulation
Zdroj: Visual Neuroscience. 23:11-24
ISSN: 1469-8714
0952-5238
DOI: 10.1017/s095252380623102x
Popis: Glutamate release from photoreceptor terminals is controlled by voltage-dependent calcium channels (VDCCs). In humans, mutations in theCacna1fgene, encoding the α1Fsubunit of VDCCs, underlie the incomplete form of X-linked congenital stationary night blindness (CSNB2). These mutations impair synaptic transmission from rod and cone photoreceptors to bipolar cells. Here, we report anatomical and functional characterizations of the retina in thenob2(no b-wave 2) mouse, a naturally occurring mutant caused by a null mutation inCacna1f. Not surprisingly, theb-waves of both the light- and dark-adapted electroretinogram are abnormal innob2mice. The outer plexiform layer (OPL) is disorganized, with extension of ectopic neurites through the outer nuclear layer that originate from rod bipolar and horizontal cells, but not from hyperpolarizing bipolar cells. These ectopic neurites continue to express mGluR6, which is frequently associated with profiles that label with the presynaptic marker Ribeye, indicating potential points of ectopic synapse formation. However, the morphology of the presynaptic Ribeye-positive profiles is abnormal. While cone pedicles are present their morphology also appears compromised. Characterizations of visual responses in retinal ganglion cellsin vivo, under photopic conditions, demonstrate that ON-center cells have a reduced dynamic range, although their basic center-surround organization is retained; no alteration in the responses of OFF-center cells was evident. These results indicate thatnob2mice are a valuable model in which to explore the pathophysiological mechanisms associated withCacna1fmutations causing CSNB2, and the subsequent effects on visual information processing. Further, thenob2mouse represents a model system in which to define the signals that guide synapse formation and/or maintenance in the OPL.
Databáze: OpenAIRE
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