Dysregulating mTORC1-4E-BP2 signaling in GABAergic interneurons impairs hippocampus-dependent learning and memory

Inhibitory neurons require optimal mTORC1 activity to promote memory formation. (A) Schematics of the hippocampus-dependent memory tests used for the study. (Left panel) Novel object location (NOL). (Middle panel) OPL. (Right panel) NOR. (B–D) Memory measured by DI of NOL, OPL, and NOR, respectively, during testing in Rptor^flx/flx:Gad2-Cre (NOL n = 10; OPL n = 12; NOR n = 13) versus Rptor^+/+:Gad2-Cre (NOL n = 12; OPL n = 11; NOR n = 13). (E–G) Memory measured by DI of NOL, OPL, and NOR, respectively, during testing in Eif4ebp2^flx/flx:Gad2-Cre (NOL n = 15; OPL n = 15; NOR n = 15) versus Eif4ebp2^+/+:Gad2-Cre (NOL n = 16; OPL n = 16; NOR n = 16). Statistical significance: (*) P < 0.05, (**) P < 0.01; (ns) not significant, calculated by an unpaired t-test. (^###) P < 0.001; (ns) not significant, calculated by a one-sample t-test. Data are presented with box and whisker plots where “+” indicates the mean. Dashed line indicates no discrimination of objects (i.e., memory impairment).