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

Abstract

<p>(<b>A</b>) Detection of <i>Mef2a</i> and <i>Mef2d</i> transcripts by <i>in situ</i> hybridization in littermate CTL and <i>Mef2a/d</i>^DKO (DKO) mice. Arrow indicates hippocampus. (<b>B</b>) Expression level of MEF2 transcription factors in the hippocampus of <i>Mef2a/d</i>^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. (<b>C</b>) <i>Mef2a/d</i>^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; <i>Mef2a/d</i>^DKO, n=10), posthoc analysis demonstrated that trial numbers 3–8 were significantly different between the <i>Mef2a/d</i>^DKO and CTL mice. (<b>D</b>) <i>Mef2a/d</i>^DKO mice show normal associative learning, as assessed by context- and cue-dependent fear conditioning (CTL, n=8; <i>Mef2a/d</i>^DKO, n=10). (<b>E</b>) 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 <i>Mef2a/d</i>^DKO mice (n=31 dendritic segments from 31 neurons of two CTL mice and n=68 dendritic segments from 68 neurons of four <i>Mef2a/d</i>^DKO mice). (<b>F</b>) CA1 LTP induction and maintenance is normal in DKO mice (CTL, n=3; <i>Mef2a/d</i>^DKO, n=3). (<b>G</b>) Input-output relations are normal in <i>Mef2a/d</i>^DKO mice (CTL, n=4; <i>Mef2a/d</i>^DKO, n=4; solid lines indicate lines of best fit.). (<b>H</b>) Paired-pulse facilitation is increased in <i>Mef2a/d</i>^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; <i>Mef2a/d</i>^DKO, n=7). All data is shown as mean ± SEM.</p