Abstract
Abstract: :
Purpose: Knockout (KO) mice lacking the RIIß subunit of PKA (RIIß KO mice), despite compensatory upregulation of PKA–RI subunits, display little or no ocular dominance plasticity (ODP; Fischer, Q.S. et al 2002, Soc. Neurosci. Abstr. 820.9). We hypothesized that this occurs because RII, but not RI subunits of PKA, are localized to relevant substrates through binding with the A–kinase anchoring protein AKAP150. Methods: To test this hypothesis we compared ODP in normal wild type, monocularly deprived (MD) wild type, MD RIIß KO, MD RIIα KO, and MD AKAP150 KO mice. On postnatal day 24 (P24) deprived mice underwent monocular lid suture. Between P28–33 extracellular single–unit recordings were made in all mice to determine the weighted ocular dominance (WOD) scores of 4–6 cells in each of 4–6 penetrations made across the mediolateral extent of binocular V1 contralateral to the deprived eye. Subsequently, genotypes were confirmed by PCR. Statistical significance between groups was assessed by t–test. Results: WOD scores in MD RIIß KO mice (mean ± std = 0.33 ± 0.09, N = 7 mice) were significantly different from those in MD (0.50 ± 0.05, N = 7 mice; p = 0.001), but not normal wild type mice (0.29 ± 0.06, N = 7 mice; p = 0.33). In contrast, WOD scores in MD RIIα KO (0.40 ± 0.06, N = 5 mice) and AKAP150 KO mice (0.37 ± 0.03, N = 5 mice) were significantly different from both normal (p = 0.008 and 0.01, respectively) and MD wild type mice (p = 0.006 and 0.0002, respectively), indicating an incomplete blockade of ODP in these mutants. Finally, WOD scores in MD RIIα KO and AKAP150 KO mice were not significantly different from each other (p = 0.44) or from MD RIIß KO mice (p = 0.19 and 0.33, respectively). Conclusions: Together these results show that both RII subunits of PKA, as well as their localization by AKAP150 is critical for ODP.
Keywords: visual cortex • plasticity • transgenics/knock–outs