Fig. 4.

The ipsCA1–conCA1 synaptic efficacy is readjusted selectively for generalization. a, b After 40-min baseline recordings for ispCA1-conCA1 fEPSP, animals were subjected to fear conditioning (FC). Control animals (CTL) were exposed to the training box without footshocks. c, d No difference from baseline (BL) was detected at 0.5 h after FC, but a reliable synaptic potentiation was found to be developed over 24 h after FC when generalization was well developed. e, f No difference from BL was found at 24 h after FC if extinction training (Ext) was applied at 0.5 h to disrupt generalization formation, while a synaptic potentiation at 24 h after FC was observed in homecage animals (HC) without Ext. g, h AAV-hsyn-hM3Dq-mCitrine was injected into ipsCA1, while guide cannula was implanted into conCA1. Application of clozapine-N-oxide (CNO group) twice, immediately after fear conditioning and 30 min before retrieval tests at 8 h via the guide cannula, enhanced generalization in a similar box (G-box), up to the levels almost equivalent to that in the training box (T-box). Without CNO treatment (saline control), the scores in G-box were significantly lower than that in T-box. Statistical comparisons are performed by using repeated one-way ANOVA d, f or two-way ANOVA h; *P < 0.05, **P < 0.01. Error bars, s.e.m. ipsCA1, ipsilateral CA1; conCA1, contralateral CA1