Figure 2.

Macroscopic Inference Network in Humans and the Necessary Contribution of dCA1 to Inference in Mice

(A) 7T fMRI used to measure the BOLD signal during the inference task (Figure 1C).

(B) Significant right hippocampal BOLD signal during correct inference (“correct” – “incorrect” inference: right, t₂₁ = 4.15, p = 0.022; left, t₂₁ = 2.80, p = 0.221; Figure S3A; Table S1).

(C) Significant BOLD signal in auditory cortex during inference test trials (“inference trials” – “conditioning trials”: t₂₁ = 14.76, p < 0.001).

(D) Psychological-physiological interaction showing differential co-activation with auditory cortex (seed region, C, Figure S3B) on correct versus incorrect inference trials (hippocampus: t₂₁ = 4.23, p = 0.015; and other regions: retrosplenial cortex: t₂₁ = 3.88, p = 0.012; visual cortex: t₂₁ = 4.77, p < 0.001; Table S2).

(E–J) In mice. Yellow, laser on; gray, laser off. (E) Schematic: ArchT-GFP viral injections, optic fibers, and tetrodes targeting dCA1 of CamKII-Cre mice for ensemble recording and manipulation. (F) dCA1 (green) ArchT-GFP expression. Scale bar, 500 μm (left), 50 μm (right). (G) Raster plot showing photo-silencing of spiking activity for an example dCA1 pyramidal cell from an ArchT-GFP mouse. (H) Light-induced changes in firing rate for simultaneously recorded dCA1 pyramidal cells in an example ArchT-GFP mouse (laser on: t₃₀ = −10.86, p < 0.001; laser off – laser on: t₃₀ = 10.88, p < 0.001). Rate changes expressed for each cell as the differences between laser on and laser off firing over the sum (scores; center line, median; box limits, upper and lower quartiles; whiskers, 1.0× interquartile range). (I and J) Left panel: schematic of light delivery. Bottom right panel: raw data points for set 1 (orange) and set 2 (green); black dot, mean; black ticks, ± SEM. Top right panel: behavioral measures of reward seeking bias shown using DABEST plots, as in Figures 1E and 1F. (I) dCA1 light delivery during auditory cues Xn in the inference test impaired reward-seeking bias in ArchT-GFP mice (set 1 – set 2: laser off p < 0.001; laser on p = 0.794; laser off – laser on: t₅₄ = 2.25, p = 0.029; alpha set to 0.05; Figure S2I) but not in GFP control mice (set 1 – set 2: laser off p < 0.001; laser on p < 0.001; laser off – laser on: t₄₆ = −0.85, p = 0.399; alpha set to 0.05). The significant reward-seeking biases (ArchT-GFP laser off; GFP control laser off and on) remained significant with Bonferroni correction for four comparisons, alpha set to 0.013. A significant interaction was also observed between the ArchT-GFP and GFP control mice (group × laser interaction, two-way ANOVA, F_1,100 = 4.42, p = 0.038). (J) dCA1 optogenetic silencing during visual cues Yn, presented after the inference task was complete, did not impair reward-seeking bias in ArchT-GFP mice (set 1 – set 2: laser off p = 0.003; laser on p < 0.001; laser off – laser on: t₂₆ = −0.14, p = 0.891).

See also Table S4.