Figure 2.

Abnormal processing of natural stimulus patterns in Fmr1 KO mice. A, Changes in synaptic strength during natural stimulus trains plotted as a function of time for WT and Fmr1 KO mice. Note the excessive increases in synaptic strength during bursts in the Fmr1 KO mice. The top shows the natural stimulus pattern used (Fenton and Muller, 1998), preceded by four and followed by six control stimuli at 0.2 Hz. n = 11 and 13 for WT and Fmr1 KO, respectively. B, Same as in A but plotted as a function of stimulus number. Inset shows EPSCs 75–83 during the natural stimulus trains, scaled to their own controls for comparison. C, Synaptic strength during natural stimulus trains (data from A) plotted as a function of instantaneous stimulus frequency, i.e., reciprocal of interspike intervals. Solid lines represent fits to a Boltzmann equation: y = (A1 − A2)/(1 + exp ((x − x₀)/dx)) + A2, where A1 is the basal gain level, A2 is the elevated gain level, and x₀ is the transition frequency. D, Normalized EPSC amplitudes during the natural spike trains in WT and KO animals are plotted point by point against each other; the correlation coefficient is determined by linear regression (blue line). Correlation analysis shows that FMRP loss alters the amplitude but not the pattern of changes in synaptic strength during natural stimulus trains. E, Average synaptic gain during natural stimulus trains plotted as a function of frequency bands. The frequency dependence of abnormal synaptic enhancement in Fmr1 KO is similar to that seen in Figure 1D during constant-frequency trains. ***p < 0.001.