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May 28, 2010

Wired for sight

Proper maturation of the visual cortex in mice, and possibly humans, depends on a maternal gene

Figure 1: Visual experience is needed to refine the nerve connections of the visual system.

credit: iStockphoto/Jack_Zhang

The copy of the gene Ube3a inherited from the mother—not the father—is crucial to proper wiring of the visual cortex in mice after birth, a RIKEN researcher and his American co-worker have found1. In human babies, a defective maternal Ube3a gene causes a developmental condition known as Angelman syndrome that leads to mental retardation, speech impairment and brain seizures, and affects behavior. The researchers therefore suggest that stimulating the silenced paternal gene at the right time of development might be worth exploring as therapy for this syndrome.

Nerve cell wiring of the visual cortex of the brain occurs after birth, and is then refined by experience (Fig. 1). Typically, images are constructed using signals from nerve cells that receive more input from one eye than the other, an occurrence known as ocular dominance (OD). The balance of OD displays plasticity; it can be altered, for instance, by temporarily blinding one eye during the critical period of development when the interconnections of nerve cells in the brain are susceptible to experience.

Masaaki Sato from the RIKEN Brain Science Institute, Wako, and Michael Stryker from the University of California, San Francisco, confirmed in mice that by about four weeks of age—their critical period of development—the presence of the Ube3a protein is mainly restricted to the nucleus of nerve cells in the visual cortex of the brain; and it is dependent on the maternal gene.

The researchers then investigated how the interconnections of the nerve cells could be changed before, during and after the critical period. They tested these changes using optical imaging, a technique that can provide information on activity in the brain. They found that both maternal and paternal copies of the gene contributed to normal development until the critical period. From this stage on, however, the maternal copy alone was active and required for maturation of the cortical circuits. Without the maternal gene the visual system did not rapidly adjust OD to the experience of having one eye briefly blinded during the critical period. And afterwards, there was impairment of the ability to make the minor wiring adjustments as the system matured.

“We now want to investigate how Ube3a participates in the maturation process of cortical neuronal circuits,” Sato says. “The other direction [of our work] will be to screen genes or compounds which have potential to restore the impaired plasticity of Ube3a maternal-deficient mice.”

References

  1. Sato, M. & Stryker, M.P. Genomic imprinting of experience-dependent cortical plasticity by the ubiquitin ligase gene Ube3a. Proceedings of the National Academy of Sciences USA 107, 5611–5616 (2010).
    (Link)