Figure 3. mAChRs mediate the learning-dependent synaptic delivery of AMPARs in CA1 pyramidal neurons.

(a) Experimental design of the inhibitory avoidance (IA) task. (b) AMPA/NMDA ratio in untrained, IA-trained or scopolamine (Sco)-pretreated IA-trained rats (2 mg kg⁻¹ i.p.). The AMPA/NMDA ratio in untrained animals was designated as 100%. Sco blocked the IA-training-dependent increase in the AMPA/NMDA ratio (**P=0.0008 versus untrained and 0.0022 versus Sco+IA trained, untrained: n=24, IA trained: n=24, Sco+IA trained: n=17, one-way factorial ANOVA followed by post hoc analysis with the Fisher’s PLSD test). Cumulative distributions of the AMPA/NMDA ratio are also shown. (c) Latency before re-entering the dark box (IA latency) in untrained, IA-trained and Sco-pretreated IA-trained rats. **P<0.0001 versus untrained (untrained: n=8, IA trained: n=9, Sco+IA trained: n=7, one-way factorial ANOVA followed by post hoc analysis with the Fisher’s PLSD test). (d) Experimental design of unilateral gene delivery (GFP-GluA1) and the IA task. Data are collected from the injected hemisphere. (e) Rectification index (RI: response at –60 mV/response at 40 mV) in untrained, IA-trained or Sco-pretreated IA-trained rats (2 mg kg⁻¹ i.p.). The RI of the CA1 pyramidal neurons expressing GFP-GluA1 (green) was normalized to that of nearby uninfected cells (black). **P=0.0003 versus uninfected (n=17, paired t-test). IA training induced synaptic delivery of the GFP-GluA1, and this delivery was blocked by Sco pretreatment P=0.40 (n=17, paired t-test). Cumulative distributions of the rectification index are also shown. The number of cells (b,e) or rats (c) in each group is shown at the bottom of each bar. Representative traces are shown in top insets. Error bars indicate ±s.e.m. Vertical scale bars, 40 pA; horizontal scale bars, 50 ms.