Genomic imprinting of experience-dependent cortical plasticity by the ubiquitin ligase gene Ube3a.
A defect in the maternal copy of a ubiqutin ligase gene Ube3a can produce a neurodevelopmental defect in human children known as Angelman syndrome. We investigated the role of the maternally expressed Ube3a gene in experience-dependent development and plasticity of the mouse visual system. As demonstrated by optical imaging, rapid ocular dominance (OD) plasticity after brief monocular deprivation (MD) was severely impaired during the critical period (CP) in the visual cortex (VC) of Ube3a maternal-deficient (m-/p+) mice. Prolonged MD elicited significant plasticity in m-/p+ mice that never matched the level seen in control animals. In older animals after the CP, 7-day MD elicited mild OD shifts in both control and m-/p+ mice; however, the OD shifts in m-/p+ mice lacked the strengthening of visual responses to the two eyes characteristic of normal adult plasticity. Anatomic effects of the maternal deficiency include reduced spine density on basal, but not apical, dendrites of pyramidal neurons in the binocular region of the VC. Imprinting of Ube3a expression was not fully established in the early postnatal period, consistent with the normal development of cortical retinotopy and visual acuity that we observed in m-/p+ mice, but was fully established by the onset of the CP. These results demonstrate that paternal and maternal genomes are not functionally equivalent for cortical plasticity, and that maternally expressed Ube3a is required for normal experience-dependent modification of cortical circuits during and after the CP.
Sato
Masaaki
M
W.M. Keck Foundation Center for Integrative Neuroscience, Department of Physiology, University of California, San Francisco, CA 94143-0444, USA.
Stryker
Michael P
MP
D017204:Angelman Syndrome / Q000235:genetics / Q000503:physiopathology; D000818:Animals; D023882:Dominance, Ocular / Q000235:genetics / Q000502:physiology; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D014793:Visual Cortex / Q000254:growth & development / Q000502:physiology*
C502429:Ube3a protein, mouse; D044767:Ubiquitin-Protein Ligases