Reduced long-term potentiation in Shank3 heterozygous mice. (A) Long-term potentiation (LTP) following high-frequency stimulation. Field recordings of LTP induced with high-frequency stimulation (HFS; 4 times 100 Hz, separated by 5 min) as a function of time in slices from wild-type and Shank3 heterozygous mice. (B) LTP following θ-burst stimulation (TBS). (C) Long-term depression (LTD) following low-frequency stimulation (LFS), an NMDA receptor-dependent form of LTD. (D) LTD following paired-pulse low-frequency stimulation (PP-LFS), a protein synthesis-dependent form of LTD. (E) LTP recorded with whole cell patch-clamp method. LTP was induced with θ-burst pairing (TBP). (E) Normalized EPSP slope is shown as a function of time. (G) Representative EPSP traces before and after (arrow) LTP induction (scale bar: 5 mV, 10 ms). (F) Changes in normalized spine volume following LTP. (H) Representative images showing TBP-induced spine expansion in Shank3 heterozygotes. Images were acquired before and 5 min and 45 min after TBP. Transiently increased and stable spines are indicated by arrowheads and arrow, respectively (scale bar: 1 μm). WT, wild-type mice; Het, Shank3 heterozygous mice.