Extended Data Fig. 6: Hippocampal dependency of novelty preference and decorrelation of CA3-CA1 firing patterns in the continuous multi-object recognition task.

(a-c) Hippocampal lesions impair novelty preference in the continuous multi-object recognition task. (a) Mice that received sham lesions (n = 8 mice) showed a strong behavioural preference for the novel object over the familiar objects (p = 0.001, two-sided paired permutation test). Mice with hippocampal lesions (n = 8 mice) showed a weaker but still significant novelty preference (p = 0.001, two-sided paired permutation test). (b) Direct comparison showed significantly stronger novelty preference in sham compared to hippocampal-lesioned mice (p = 0.005, two-sided permutation test). (c) Example histology of coronal brain sections from one sham-lesioned and one hippocampal lesioned mouse (with anterior-posterior position from bregma above each section). (d) Behavioural experience of novel objects is associated with reduced CA3-CA1 ensemble co-firing. Using ensemble recordings during behavioural sampling of novel objects (blue letters), we found that CA3-CA1 pair-wise firing correlations were significantly lower compared to those measured during exploration of a familiar (circular-walled) environment without objects (p = 0.002, two-sided paired permutation test, n = 1721 CA3-CA1 cell-pairs in 7 mice). Upper panel: each data point represents the correlated activity of one-pair of simultaneously recorded CA3-CA1 PCs. Lower plot: median difference between co-firing in novel object sampling minus familiar arena. Notably, this finding shows that processing of new information is naturally associated with a decorrelation of CA3-CA1 firing patterns. Panels a-b,e show Cumming estimation plots as described in Extended Data Fig. 1e. ***p < 0.001, **p < 0.01.