Bidirectional regulation of Munc13–3 protein expression by age and dark rearing during the critical period in mouse visual cortex

Abstract

Rearing in darkness slows the time course of the visual cortical critical period, such that at 5 weeks of age normal cats are more plastic than dark-reared cats, while at 20 weeks dark-reared cats are more plastic (Mower, Dev. Brain Res., 58: 151-158, 1991). Thus, genes that are important for visual cortical plasticity should show differences in expression between normal and dark-reared visual cortex that are of opposite direction in young versus older animals. Previously, we showed by differential display PCR and northern blotting that mRNA for Munc13-3, a mammalian homologue of the C. elegans uncoordinated (unc) gene, shows such bidirectional regulation in cat visual cortex (Yang et al., J. Neurosci., 22: 8614-8618, 2002). Here, the analysis is extended to Munc13-3 protein in mouse visual cortex, which will provide the basis for gene manipulation analysis. In mice, Munc13-3 protein was elevated 2.3 fold in dark-reared compared to normal visual cortex at 3.5 weeks and 2.0 fold in normal compared to dark-reared visual cortex at 9.5 weeks. Analysis of variance of protein levels showed a significant interaction, indicating that the effect of dark rearing depended on age. This bidirectional regulation was restricted to visual cortex and did not occur in frontal cortex. Bidirectional regulation was also specific to Munc13-3 and was not found for other Munc13 family members. Munc13 proteins serve a central priming function in synaptic vesicle exocytosis at glutamatergic and GABAergic synapses and this work contributes to the growing evidence indicating a role of Munc13 genes in synaptic plasticity.

Genes and pathways underlying regional and cell type changes in Alzheimer's disease

“…Furthermore, increasing expression of ABCA1 with increasing severity of AD has been measured both functionally and neuropathologically [43]. Although none of the neuroprotective genes have known roles in AD, two have been associated with neuroprotection or plasticity in other contexts: variants of LINGO2 have been associated with risk and age of onset in Parkinson's disease [44], while UNC13C is a candidate gene for critical period neuronal plasticity in visual cortex [45]. …”

Munc13-3 Superprimes Synaptic Vesicles at Granule Cell-to-Basket Cell Synapses in the Mouse Cerebellum

“…the visual cortex, in which Munc13-3 expression is tightly correlated with the critical period (Yang et al, 2007), Munc13-3 may shape the network characteristics of the mature cerebellar cortex. GCs respond to sensory stimulation with brief bursts of APs (Chadderton et al, 2004), for which changes in p r induce a redistribution of synaptic efficacy within the burst (Markram and Tsodyks, 1996).…”

Roles of the fission yeast UNC-13/Munc13 protein Ync13 in late stages of cytokinesis

“…Munc13-3 is expressed in the visual cortex for neuronal plasticity besides its function in the cerebellum ( Yang et al. , 2002 ; Yang, Kiser, et al. , 2007 ; Netrakanti et al.…”