Extended Data Fig. 3: GABAergic hypnotic agents induce net suppression of L2/3 pyramidal cell activity.
From: Ketamine triggers a switch in excitatory neuronal activity across neocortex
(a, b) Representative GCaMP6 traces of individual L2/3 neurons under wakefulness and different hypnotic agents (a, sevoflurane (sevo), yellow shaded region; b, midazolam (midaz), green shaded region). (c) (Left) Line scatterplots and (Right) box plots of average spontaneous rate of L2/3 activity before and after volatile (sevo or isoflurane/iso, purple) and midaz hypnosis in S1. Spontaneous activity: Sevo group (71 neurons from 4 mice), awake: 4.0 ± 0.8 vs. Sevo: 1.0 ± 0.4, P = 2.8 × 10−8; Iso group (78 neurons from 7 mice), awake: 2.4 ± 0.5 vs. Iso: 0.1 ± 0.1, P < 1 × 10−15; Midaz group (85 neurons from 3 mice), awake: 2.8 ± 0.6 vs. Midaz: 0.4 ± 0.1, P = 4 × 10−15). (d) Peak ΔF/F0 before and after hypnosis (Sevo: awake: 238 ± 30% vs. Sevo: 47 ± 5%, P = 2.9 × 10−10; Iso: awake: 102 ± 12% vs. Iso: 14 ± 0.5%, P < 1 × 10−15; Midaz: awake: 83 ± 7% vs. Midaz: 30 ± 2%, P = 5.6 × 10−12). Same cells from c. (e) Relative change in L2/3 activity for different hypnotic agents. Unlike KET, GABAergic hypnotics induced a uniform suppression of L2/3 neuronal activity (fraction of cells with reduced activity under GABAergic agents 65–78% vs. KET ~40%). While KET induced substantial activation of the network (~40–45% of cells), GABAergic agents activated fewer than 10% of cells. Box and whisker plot show min to max, centre (median), 25th and 75th percentile box bounds. One-sided Kruskal-Wallis with Dunn’s multiple comparisons test in c, d, ***P < 0.001.
