Abnormal synaptic transmission in the hippocampi of Shp2 cKO mice. Synaptic transmission was examined at Schaffer collateral-CA1 synapses in hippocampal slices prepared from Shp2flox/flox (control [Ctrl]) or Shp2 cKO mice at 14 to 20 weeks of age. (A) Relationship between fiber volley amplitude and fEPSP slope (I/O relationship) for basal synaptic transmission examined over a range of stimulus intensities (1 to 6 V). The slope of the I/O curve was calculated for each slice for statistical analysis. (B) Ratio of the second to the first fEPSP slope (PPR) for PPF evoked by delivery of two stimuli with a short interstimulus interval. Sample traces show averages of three fEPSPs at an interstimulus interval of 50 ms. Calibration: 20 ms, 0.2 mV. **, P < 0.01 versus the corresponding control value (Student's t test). (C) fEPSP slope before (baseline) and after induction of LTP by tetanic stimulation (100 Hz, 1 s). Data are expressed as percentages of the baseline value. Sample traces show averages of three fEPSPs recorded before (1, thin lines) and after (2, thick lines) LTP induction. Calibration: 5 ms, 0.5 mV. (D) fEPSP slope examined as in panel C but in the presence of 50 μM APV. Sample traces show fEPSPs recorded before (1, thin lines) and after (2, thick lines) PTP induction. Calibration: 5 ms, 0.5 mV. All data are mean values ± SEM (n = 6 to 18 slices from three or four mice).