Metabotropic glutamate receptor-dependent long-term depression is impaired due to elevated ERK signaling in the ΔRG mouse model of tuberous sclerosis complex

► Mutations in TSC2-GAP domain disrupt hippocampal mGluR-LTD in ΔRG mice. ► ΔRG mice exhibit normal mTORC1 signaling, but enhanced ERK signaling. ► Impaired hippocampal mGluR-LTD is due to aberrant MEK/ERK signaling in ΔRG mice. ► Mice with conditional deletions of the Tsc1 and Tsc2 genes exhibit deficits in mGluR-LTD, but normal MEK/ERK signaling.