Brain-specific deletion of Mef2a and Mef2d causes impairments in motor coordination, as well as presynaptic release probability.

(A) Detection of Mef2a and Mef2d transcripts by in situ hybridization in littermate CTL and Mef2a/d^DKO (DKO) mice. Arrow indicates hippocampus. (B) Expression level of MEF2 transcription factors in the hippocampus of Mef2a/d^DKO mice as detected by quantitative RT-PCR. RNA was isolated from the hippocampus of 4 week old animals (n=3/genotype), and then expression determined by quantitative PCR. The fold change in RNA was calculated using the comparative Ct method, normalizing to GAPDH as a control. (C) Mef2a/d^DKO mice exhibit impaired motor coordination as assessed by falling off the accelerating rotarod faster than littermate CTLs (F_1,7=27.64, P<0.05; CTL, n=8; Mef2a/d^DKO, n=10), posthoc analysis demonstrated that trial numbers 3–8 were significantly different between the Mef2a/d^DKO and CTL mice. (D) Mef2a/d^DKO mice show normal associative learning, as assessed by context- and cue-dependent fear conditioning (CTL, n=8; Mef2a/d^DKO, n=10). (E) Representative images of Golgi-stained CA1 pyramidal neurons and a bar graph comparing the number of dendritic spines per 10 µm length of dendrite from littermate CTL and Mef2a/d^DKO mice (n=31 dendritic segments from 31 neurons of two CTL mice and n=68 dendritic segments from 68 neurons of four Mef2a/d^DKO mice). (F) CA1 LTP induction and maintenance is normal in DKO mice (CTL, n=3; Mef2a/d^DKO, n=3). (G) Input-output relations are normal in Mef2a/d^DKO mice (CTL, n=4; Mef2a/d^DKO, n=4; solid lines indicate lines of best fit.). (H) Paired-pulse facilitation is increased in Mef2a/d^DKO mice at Inter-Stimulus Interval 20, 30, 50, 100, 200 and 400 (mS) compared to littermate CTLs, suggesting decreased presynaptic release probability (CTL, n=8; Mef2a/d^DKO, n=7). All data is shown as mean ± SEM.