Extended Data Fig. 9: Validation of 5-HT2A receptor knockout in experimental models.
From: Psilocybin’s lasting action requires pyramidal cell types and 5-HT2A receptors
a, Example sEPSC traces from 5 GFP+ layer 5 pyramidal neurons, with each set of 3 traces coming from recording of the same cell, including baseline (black), after bath application of 20 μM 5-HT (red), and after bath application of 20 μM 5-HT with 100 nM MDL100,907 (grey). Cells 1 and 2 are from control animals. Cells 3, 4, and 5 are animals with local 5-HT2A receptor knockout. b, Mean sEPSC amplitude from GFP+ layer 5 pyramidal neurons for baseline, 20 μM 5-HT, and 20 μM 5-HT + 100 nM MDL100,907 conditions, for control mice (grey) and local 5-HT2A receptor knockout mice (blue). Circle, individual cell. Mean and s.e.m. across cells. n = 22 cells (Baseline), n = 22 cells (+5-HT), n = 6 cells (+5-HT + MDL) from 4 mice in the Control condition, n = 23 cells (Baseline), n = 23 cells (+5-HT), n = 7 cells (+5-HT + MDL) from 4 mice in the 5-HT2AR local KO condition. c-e, Constitutive Camk2acre;Htr2af/f mice had reduced Htr2a transcripts and fewer psilocybin-induced head-twitch response. c, Breeding scheme to generate Camk2acre;Htr2af/f mice. d, Transcript expression via qPCR from whole-brain tissue. n = 2 (Control), n = 3 (Camk2acre;Htr2af/f). e, Head-twitch response induced by psilocybin (1 mg/kg, i.p.). Mean and s.e.m. across mice. n = 11 (Control), n = 12 (Camk2acre;Htr2af/f). ** p < 0.01. Detailed sample size n values are provided in Methods. Statistical analyses are provided in Supplementary Table 1.
