title: Virally mediated knock-down of NR2 subunits ipsilateral to the deprived eye blocks ocular dominance plasticity.
abstract: NMDA receptors (NMDARs) are important in developmental plasticity in the visual cortex. The NR2A and NR2B subunits of this receptor develop with different time courses, suggesting that they play different roles in plasticity. To understand the role of the NR2B subunit, we knocked-down NR2B gene expression in visual cortex by injecting a recombinant adenovirus containing an antisense NR2B oligonucleotide. To assess knock-down, we injected the recombinant adenovirus into the right visual cortex of rats (p22) or mice (p30). Eight days later we perfused the animals and processed the visual cortex for NMDAR subunit immunoreactivity (IR). NR2B-IR was depleted dramatically in the neuropil near the injection. Depletion was more modest in the neuronal somata. Surprisingly, NR2A-IR was also reduced, but NR1-IR was not reduced. To assess the functional effects of depletion, we measured ocular dominance plasticity with monocular deprivation (MD). We compared mice receiving the NR2B antisense virus with mice receiving virus containing only the GFP sequence and mice receiving no injection. All injections were between p26 and p29 in the right cortex and bilateral recordings were performed 6-8 days later. Animals receiving the antisense virus lost plasticity if the right eye was deprived. If the left eye was deprived, the cortex was normally plastic bilaterally. Injection of control virus had no effect on plasticity. The data indicate that ocular dominance plasticity requires normal NMDARs in the hemisphere ipsilateral to the deprived eye but not in the hemisphere contralateral to the deprived eye.
authors.affiliation: Portland VA Medical Center, PO Box 1034/P3ANES, Portland, OR 97239, USA.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Cao
authors.forename: Lijuan
authors.initials: L
authors.lastname: Liu
authors.forename: Marvin
authors.initials: M
authors.lastname: Lickey
authors.forename: Aundrea
authors.initials: A
authors.lastname: Graves
authors.forename: Tony
authors.initials: T
authors.lastname: Pham
authors.forename: Barbara
authors.initials: B
authors.lastname: Gordon
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology; D023882:Dominance, Ocular / Q000235:genetics* / Q000502:physiology*; D005074:Evoked Potentials, Visual / Q000502:physiology; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics* / Q000502:physiology*; D019581:Neuropil / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic; D014793:Visual Cortex / Q000502:physiology
chemical_list: C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016376:Oligonucleotides, Antisense; D016194:Receptors, N-Methyl-D-Aspartate; D049452:Green Fluorescent Proteins