IGF-1 reverses deficits in LTP, AMPA signaling, and motor function in Shank3 -deficient mice. Wild-type (WT) and heterozygous (Het) mice were treated with saline or recombinant human IGF-1 (rhIGF-1) for 2 weeks (beginning at PND 13 to 15) before testing and analyzed immediately after the last injection. Methods for all experiments were as described previously [5, 7], with 4 to 9 mice per group. (a) Hippocampal LTP was induced with high-frequency stimulation. Inset: Representative excitatory postsynaptic potential traces at 90 min after LTP induction from saline-injected (1) and rhIGF-1-injected (2) heterozygous mice (scale bar: 0.5 mV, 10 ms). (b) Slices were incubated in the presence of the N-Methyl-D-aspartate (NMDA) antagonist R-2-amino-5-phosphonopentanoate (APV) to expose AMPA receptor signaling. (c) Mice were tested for motor performance and motor learning by measuring latencies to fall off a rotating rod over three trials. Het: heterozygous; LTP: long-term potentiation; NMDA: N-Methyl-D-aspartate; rhIGF-1: recombinant human IGF-1; WT: wild-type.