Fig. 4.
GR-PO4 is required for training-evoked plasticity in motor cortex. (A) Field potential recordings of high-frequency stimulation (HFS)–induced LTP in M1 cortical slices as a function of genotype and training for 2 d on the rotarod. Acute slices on the next day of training are stimulated with half the intensity to reach a maximal response in L2 parallel fibers at a distance ≈500 μm from the recording electrodes in L2 of M1 cortex. There is a 20-min baseline recording between HFSs. (B) FP recordings of tetanus-induced LTP in M1 cortical slices from eight WT and five KI trained mice and five WT and six KI untrained mice. Means are normalized to baseline ± SEM. (C) Averaged field potential (FP) amplitudes after three consecutive HFSs (mean of last 40 min per epoch ± SEM). LTP occlusion after HFS3 by unpaired t test in WT mice (*P = 0.034). Three-way ANOVA: effect of HFS (F3,80 = 13.16, P < 0.0001), genotype (F1,80 = 4.57, P < 0.05), and genotype × training (F1,80 = 14.18, P < 0.005); post hoc Tukey test (#P = 0.011). (D) Working model. Training in WT but not KI mice occluded LTP saturation. The dashed line represents baseline transmission in M1. (E) Weaker LTP occlusion in KI mice corresponded to poorer retention of motor skills. Motor skill retention and LTP saturation indexes are described in Methods. Effect of genotype on LTP occlusion by unpaired t test (P = 0.0055) (mean ± SEM [t(14) = 3.28], n = 8 mice per group) and on motor skill retention (P = 0.014) (mean ± SEM [t(22) = 2.64], n = 12 mice per group).