Research Paper Volume 9, Issue 5 pp 1386—1403

Transgenic autoinhibition of p21-activated kinase exacerbates synaptic impairments and fronto-dependent behavioral deficits in an animal model of Alzheimer’s disease

Figure 4. Reducing PAK activity counteracts the enhancement of the glutamatergic synaptic tone observed in 3xTg-AD mice. (A) Experimental design for patch clamp recordings of layer II/III pyramidal cells of the medial prefrontal cortex. (B) While the mean frequency of mEPSCs was comparable between the three genotypes, the mean amplitude of mEPSCs was larger in 3xTg-AD mice. This phenomenon was not present in 3xTg-AD-dnPAK mice. (n=5 to 6 cells per group), **p<0.01, oop<0.01, Fisher LSD post hoc test (C and D). A significant reduction in GAD65 and VGAT expression was observed in both 3xTg-AD and 3xTg-AD-dnPAK animals when compared with NonTg animals (N=12-13 mice for NonTg, N=19-21 mice for 3xTg-AD and N=16-17 mice for 3xTg-AD-dnPAK). Examples of Western blots were taken from the same immunoblot experiment for each primary antibody, on the same gel but run in a random order, and rearranged in the same order as the graphs (separated by black lines). **p<0.01, one way ANOVA Tukey-Kramer post hoc test.