Male and female mice performed auditory-visual induced mediated learning.

A) Schematic representation of the LTSPC task highlighting the experimental differences in male (2 training sessions during conditioning) and female (1 training session) mice. The percentage of time spent freezing during OFF and ON periods of the probe test 1 (Tone) (B) and probe test 2 (light) (D). The percentage of change of the OFF vs ON periods of the probe test 1 (Tone) (C) and probe test 2 (light) (E). GLM: generalized linear model fitted to gamma distribution with planned comparisons (B, D), * significant p-value (<0.05) after false discovery rate (FDR). Mann-Whitney between sexes (C, E) and # significant against 0 after tested by Wilcoxon test with zero method. See statistical details in Supplementary Table 1.

Simultaneous associations between light and tone are required for mediated learning formation.

(A) Schematic representation of the LTSPC task in males (2 training sessions) and females (1 training session) with a representation of paired, unpaired and no-shock experimental groups. The percentage of time spent freezing during OFF and ON periods of the probe test 1 (Tone) (B in males, C in females) and probe test 2 (light) (D in males, E in females). The percentage of change of the OFF vs ON periods of the probe test 1 (Tone) (B in males, C in females) and probe test 2 (light) (D in males, E in females). * significant p-value (<0.05) after false discovery rate (FDR). GLM: generalized linear model fitted to gamma distribution with planned comparisons. KW: Kruskal-Wallis across experimental groups: paired, unpaired, no-shock. # significant against 0 after Wilcoxon test with zero method. See statistical details in Supplementary Table 1.

Hippocampal cells during LTSPC.

A) Schematic representation of LTSPC task while fiber photometry recordings of RCaMP (calcium sensor in synapsin-positive neurons) and Cre-dependent GCaMP (calcium sensor in PV-positive interneurons) in dHPC and vHPC of PVcre mice. B) dHPC modulation during preconditioning of LTSPC: on the left upper panel z scores of (where f represents fluorescence) of GCaMP PV-positive interneurons on dHPC (green), left bottom z scores of of RCaMP in neurons of dHPC (red), right upper number of events with a of GCaMP PV-positive interneurons on dHPC, and right bottom number of trials with a of Rcamp in neurons of dHPC. C) vHPC modulation during LTSPC: on left upper painel z scores of of GCaMP PV-positive inter neurons of vHPC (green), left bottom z scores of of RCaMP in neurons of vHPC (red), right upper number of trials with a of Gcamp in PV-positive interneurons of vHPC, and right bottom number of trials with a of RCaMP in neurons of vHPC. D) maximal value of in the first 1 second window after pairings compared with baseline, on the left (dHPC) and on the right (vHPC). * significant p-value (<0.05). See statistical details in Supplementary Table 1.

Chemogenetic modulation of dorsal and ventral hippocampus during LTSPC.

A) Schematic representation of LTSPC task combined with chemogenetic approaches, where an inhibitory DREADD was infused in dHPC (representative image on the left) and vHPC (representative image on the right). During the preconditioning (DPC) or the probe test (DPT), a DREADD agonist (J60) was injected intraperitoneally (controls where injected with the agonist in both phases) (diagram of DREADD agonist administration on the center). B, C) The percentage of time spent in freezing during OFF and ON periods (left) and the percentage of change (right) of the OFF vs ON periods of the Probe Test 1 (Tone) of animals infused in dHPC (B) and vHPC (C): controls (Controls_d_Off and controls_d_On, Controls_v_Off and controls_v_On), DPC (DPC_d_Off and DPC_d_On, DPC_v_Off and DPC_v_On) and DPT (DPT_d_Off and DPT_d_On, DPT_v_Off and DPT_v_On). D, E) The percentage of time spent in freezing during OFF and ON periods (left) and the percentage change (right) of the OFF vs ON periods of the probe test 2 (Light) of animals infused in dHPC (D) and vHPC (E): controls_d, DPC_d, DPT_d and controls_v, DPC_v, DPT_v). *significant p-value (<0.05) after false discovery rate (FDR). GLM: generalized linear model fitted to gamma distribution with planned comparisons (B, D, F, H). KW: Kruskal-Wallis across experimental groups: controls, DPC, DPT (C, E, G, I). # significant against 0 after Wilcoxon test with zero method. See statistical details in Supplementary Table 1.