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The Journal of Neuroscience, January 7, 2004, 24(1):161-169; doi:10.1523/JNEUROSCI.3234-03.2004
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Development/Plasticity/Repair
Functional and Genomic Changes in the Mouse Ocular Motor System in Response to Light Deprivation from Birth
Colleen A. McMullen, Francisco H. Andrade, andJohn S. Stahl Department of Neurology, Case Western Reserve University and University Hospitals of Cleveland, Cleveland, Ohio 44106
Previous studies have suggested that abnormal visual experience early in life induces ocular motor abnormalities. The purpose of this study was to determine how visual deprivation alters the function and gene expression profile of the ocular motor system in mice. We measured the effect of dark rearing on eye movements, gene expression in the oculomotor nucleus, and contractility of isolated extraocular muscles. In vivo eye movement recordings showed decreased gains for optokinetic and vestibulo-ocular reflexes, confirming an effect of dark rearing on overall ocular motor function. Saccade peak velocities were preserved, however, arguing that the quantitative changes in these reflexes were not secondary to limitations in force generation. Using microarrays and quantitative PCR, we found that dark rearing shifted the oculomotor nucleus transcriptome to a state of delayed/arrested development. The expression of 132 genes was altered by dark rearing; these genes fit in various functional categories (signal transduction, transcription/translation control, metabolism, synaptic function, cytoskeleton), and some were known to be associated with neuronal development and plasticity. Extraocular muscle contractility was impaired by dark rearing to a greater extent than expected from the in vivo ocular motility studies: changes included decreased force and shortening speed and evidence of abnormal excitability. The results indicate that normal development of the mouse ocular motor system and its muscles requires visual experience. The transcriptional pattern of arrested development may indicate that vision is required to establish the adult pattern, but it also may represent the plastic response of oculomotor nuclei to abnormal extraocular muscles.
Key words: saccades; optokinetic reflex; vestibulo-ocular reflex; gene expression profiling; extraocular muscles; ocular motor system; eye movements
Received May 31, 2003; revised October 27, 2003; accepted October 28, 2003.
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