Identification of Munc13-3 as a candidate gene for critical-period neuroplasticity in visual cortex.

The first several months of life are a critical period for neuronal plasticity in the visual cortex during which anatomic and physiological development depends on visual experience. In cats, electrophysiologically assessed neuronal plasticity is minimal until approximately 3 weeks, peaks at 5 weeks, gradually declines to low levels at 20 weeks, and disappears at approximately 1 year of age (Daw, 1994). Rearing in darkness slows the entire time course of this critical period, such that at 5 weeks of age, normal cats are more plastic than dark-reared cats, whereas at 20 weeks, dark-reared cats are more plastic (Mower, 1991; Beaver et al., 2001). Thus, a stringent criterion is that genes that are important for plasticity in visual cortex will show differences in expression between normal rearing and dark rearing that are of opposite direction in young versus older animals. The present study reports the identification by differential display PCR of Munc13-3, a mammalian homolog of the Caenorhabditis elegans "uncoordinated" gene (unc-13), as a candidate gene for critical-period neuronal plasticity, the expression of which is regulated according to this criterion specifically in visual cortex and not in frontal cortex. Other members of the Munc13 family (Munc13-1 and Munc13-2) do not meet this criterion in visual cortex, indicating that Munc13-3 is the only family member that is regulated by age and dark rearing in the same manner as physiological plasticity during the visual cortical critical period.