Fig. 6: Simultaneous reactivation of multiple engram cell ensembles. | Nature Communications

Fig. 6: Simultaneous reactivation of multiple engram cell ensembles.

From: Brain-wide mapping reveals that engrams for a single memory are distributed across multiple brain regions

Fig. 6

a Labeling strategy using c-Fos-tTA and TRE-hM3Dq-mCherry in wild-type mice. b Behavioral schedule. One day after training, a natural recall test was performed (Test). The next day, mice received CNO intraperitoneally 45 min before a chemogenetic reactivation (Engram activation) session in a neutral context B. c Hippocampal DG section showing cFos+ neurons labeled with hM3Dq-mCherry. Natural memory recall (Test). Chemogenetic reactivation (Engram activation). mCherry and hM3Dq-mCherry (n = 11 mice per group) groups. d Hippocampal CA1, BLA, AM thalamus, and RE thalamus sections showing cFos+ neurons labeled with hM3Dq-mCherry. e Chemogenetic manipulation of CA1 engram cells. Natural recall (Test). Chemogenetic reactivation (Engram activation). mCherry and hM3Dq-mCherry (n = 11 mice per group) groups. f Chemogenetic manipulation of CA1 and BLA engram cells. Natural recall (Test). Chemogenetic reactivation (Engram activation). mCherry and hM3Dq-mCherry (n = 11 mice per group) groups. g Chemogenetic manipulation of CA1, BLA, and AM engram cells. Natural recall (Test). Chemogenetic reactivation (Engram activation). mCherry and hM3Dq-mCherry (n = 11 mice per group) groups. h Chemogenetic manipulation of CA1, BLA, AM, and RE engram cells. Natural recall (Test). Chemogenetic reactivation (Engram activation). mCherry and hM3Dq-mCherry (n = 11 mice per group) groups. Dashed line indicates natural recall freezing level (c, e–h). One-way ANOVA followed by Tukey multiple comparison post-hoc tests revealed significant differences between one ensemble (CA1) vs. two ensemble (CA1 and BLA) reactivations (P < 0.05), and two ensemble (CA1 and BLA) vs. three ensemble (CA1, BLA, and AM) reactivations (P < 0.05). Three ensemble (CA1, BLA, and AM) vs. four ensemble (CA1, BLA, AM, and RE) reactivations were not significantly different. Reactivation of additional engram cell ensembles correlates with enhanced memory reactivation. Unless specified, statistical comparisons are performed using two-tailed unpaired t-tests; ***P < 0.001. Data are presented as mean ± SEM. P values for activation sessions: 0.0002 (c), 6.95E−05 (e), 5.87E−07 (f), 8.75E−11 (g), 9.28E−10 (h). Source data are provided as a Source Data file. Each experiment was performed in two independent batches that yielded similar results.

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