Physiological and behavioral alterations in forebrain-specific Atg7 -deficient mice. (a-c) Forebrain-specific Atg7 cKO mice display normal basal synaptic transmission but impaired LTP of the Schaffer collateral tract. Extracellular recording of field potentials was performed at area CA1 of acutely prepared hippocampal slices from 3-month-old male CamK-Atg7 cKO mice and CamK-Atg7 cWT littermates. a, Plots of fEPSP slope (normalized to maximal) versus stimulus intensity. There was no significant difference in baseline synaptic transmission between CamK-Atg7 cKO mice and CamK-Atg7 cWT littermates. n = 12 slices from 3 mice per genotype. b, Paired-pulse facilitation in CamK-Atg7 cKO mice. The percent facilitation, determined by the ratio of the second fEPSP initial slope to the first fEPSP initial slope, is shown at interpulse intervals from 10 to 300 ms. n = 12 slices from 3 mice per genotype. c, Impaired LTP in CamK-Atg7 cKO mice. Stable baseline responses were recorded prior to HFS (100 Hz HFS for 1 s) as indicated by arrow. One train of 100 Hz HFS elicited E-LTP in CamK-Atg7 cKO mice that was decreased compared with that evoked in CamK-Atg7 cWT mice. Open squares, CamK-Atg7 cWT; Filled squares, CamK-Atg7 cKO. n = 12 slices from 3 mice per genotype. p < 0.01 by repeated measures ANOVA. (d-e) Impaired fear memory of forebrain-specific Atg7 cKO mice. d, CamK-Atg7 cKO mice showed significant impairment in contextual fear memory 24 h after the training. e, CamK-Atg7 cKO mice had impaired cued fear memory in the third day. Freezing level before the cue (tone) was not altered in CamK-Atg7 cKO mice relative to CamK-Atg7 cWT littermates (‘Pre-Test’). White bars, CamK-Atg7 cWT (n = 10); Black bars, CamK-Atg7 cKO (n = 8). *, P < 0.05. **, P < 0.01.