a, eIF4E transgenic mice (4E Tg) exhibit increased mEPSC frequency and b, increased mIPSC amplitude in layer 2/3 mPFC pyramidal neurons. n=27–30 neurons/genotype, *p<0.05 vs WT, Student's t-test. c,d, 4E Tg mice exhibit increased dendritic spine density in layer 2/3 mPFC pyramidal neurons. High-magnification images c, and quantification d, of spiny dendrites from wild-type (WT) and 4E Tg mice. n= 12 neurons/genotype, *p<0.05 vs WT, Student's t-test. Scale bar = 2 µm. e, 4E Tg mice exhibit enhanced striatal LTD. n=13 slices from 8 mice/genotype. f, 4E Tg mice exhibit enhanced hippocampal mGluR-LTD. n=15 slices from 8 mice/genotype. g, h, 4EGI-1 normalizes enhanced striatal LTD displayed by 4E Tg mice h, without impacting LTD in WT mice g. n=18 slices from 9 mice/genotype/treatment. All field recordings were analyzed with repeated measure ANOVAs. Arrows indicate delivery of high-frequency stimulation (HFS). Solid bars indicate the duration of bath application of DHPG (10 µM, 10 min) and 4EGI-1 (100 µM, 45 min). Representative traces (right panels) showing fEPSP before (black) and 60 min after (red) HFS. All data are shown as mean ± SEM.