Extended Data Fig. 8: Systemic administration of CNO does not impair ketamine’s neuronal activity switch in L2/3 neurons of S1.
From: Ketamine triggers a switch in excitatory neuronal activity across neocortex
(a) Coronal slices (left) of S1 region from interneuron-specific Cre-positive mice expressing DREADD variant hM3D(Gq)-mCherry. Scale bar: 100 µm. (Right) Number of hM3D(Gq)-mCherry positive cells in a 1 mm2 region of forelimb S1 (slice thickness 30 µm). 15 (SST), 16 (PV), and 16 (VIP) S1 slices from 4 mice in each group. Box and whisker plot show min to max, centre (median), 25th and 75th percentile box bounds. (b) Coronal slice of S1 region from mouse expressing AAV-hSynapsin-1-tdTomato. Scale bar: 100 µm. (c) Representative traces of L2/3 pyramidal cells under wakefulness, CNO, then KET at 50 mg/kg in mice expressing AAV-hSynapsin-1-tdTomato. (d) L2/3 cell activity in the setting of CNO vs. its response to KET at 50 mg/kg in mice expressing AAV-hSyn1-tdTomato (97 neurons from 3 mice). KET at 50 mg/kg induced a strong neuronal switch (Pearson correlation r = −0.68, P = 2 × 10−14) and a significant elevation in activity switch index (KET 4.9 ± 0.5) whereas CNO injection did not (1.8 ± 0.2, P > 0.05). (e) Spontaneous rate of activity of L2/3 pyramidal neurons before/baseline (BL), after interneuron subtype activation (CNO activation of hM3D(Gq)) and following KET treatment at 50 mg/kg. Same cells from Fig. 6d. One-sided Kruskal-Wallis, P < 0.001 with Dunn’s multiple comparisons and P values listed in graph. Representative images and traces carried out on at least 3 animals per group. Error bars show s.e.m. *P < 0.05, **P < 0.01, ***P < 0.001.
