The cellular and circuit mechanisms that produce dissociated states — in which an individual’s internal experiences disconnect from the environment — are unclear. Now, Cichon et al. show that, in mice, ketamine-induced dissociated states are triggered by populations of active or silent cortical pyramidal neurons switching their activity state, a phenomenon that requires the suppression of parvalbumin (PV+) and somatostatin (SST+) interneurons and is mediated by inhibition of NMDA receptors and HCN channels.