Extended Data Fig. 6: Ongoing assemblies and sound-evoked responses overlap under ketamine-medetomidine and zolazepam-tiletamine anesthesia.
From: Awake perception is associated with dedicated neuronal assemblies in the cerebral cortex
a, For an example recording session, Pearson’s correlation matrix between spontaneous assemblies sorted by hierarchical clustering and single trial sound response patterns (whether or not a population event was detected), sorted sound by sound (12 trials/sound). Clustering is done independently in pre- and post-stimulation periods. Lower correlation inside black and orange frames (similarity) compared to correlations along the diagonal (reproducibility) indicate that spontaneous and evoked patterns are different. b, Correlation matrix under ketamine (50 mg/kg) medetomidine (1 mg/kg) anesthesia (KM) for the same neuronal population as in a. Similar correlation in black and orange frames (similarity) and in the squares along the diagonal (reproducibility) indicate that spontaneous and evoked assemblies are highly similar. c, Relation between reproducibility (abscissa) and similarity (ordinate) of sound-evoked and spontaneous patterns for the 50 sounds and 6 sessions recorded in 3 mice. The unity line in black. Regression line in blue. d, Same as in c, but under KM anesthesia. e-f, Same as in c, d, but for 3 experiments in 3 different mice for Zoletil® (70 mg/kg) anesthesia. g, Slope of the regression lines in c-f. Box plot indicates the 5% confidence interval obtained by bootstrapping 1000 times across data points. For both anesthetics, the bootstrap p-value was <0.001. h, Mean difference between reproducibility and similarity in c-f. The bootstrap p-value was <0.001 for KM and 0.02 for Zoletil. In boxplots of g-h, the central mark indicates the median, and the bottom and top edges of the box indicate the 25th and 75th percentiles, respectively. Distributions were obtained by bootstrapping across data points. The whiskers extend to the most extreme data points. Bootstrapping (1000 random resampling with replacement) was also used to assess the significance of the difference between slopes obtained in anesthesia and in wakefulness. For both anesthetics, the bootstrap p-value was <0.001. For KM anesthesia, the difference between awake and anesthetized was also significant when testing across the 6 sessions (Wilcoxon rank sum test, p = 0.03). Note that the higher slopes observed here in the awake state compared to the results shown in Fig. 2 are likely due to the smaller field of views used in KM and Zoletil® experiments (see Methods), which reduced the variety of assembly configurations and therefore the distance between assemblies. Note also that, in Zoletil anesthesia, reproducibility of sound responses was higher on average than their similarity with spontaneous activity; however, this effect was restricted to less reproducible sound response patterns, and most reproducible sound responses were similar to spontaneous activity as seen in isoflurane and KM anesthesia. This is in contrast with the awake state in which most reproducible sound responses are clearly distinct from spontaneous activity. The clear change between awake and Zoletil® anesthesia for most reliable responses is better captured by the slope measurements in g. (KM, ketamine medetomidine; spont. pre., spontaneous pre-stimulation; *,*** indicate p < 0.05, p < 0.001 respectively). All tests are two-sided.
