Single-nucleus RNA-Seq

Psilocybin is a psychedelic whose metabolite, psilocin, is a 5-HT2A receptor agonist. Nevertheless, the underlying mechanisms for the therapeutic effect of psilocybin are not fully illustrated, and cell-type-specific and circuit effects of it are not fully understood. Here, we combined single-nucleus RNA-seq with functional assays to study the long-term effects of psilocybin on the orbitofrontal cortex (OFC), a brain region vulnerable to brain disorders such as depression. We demonstrated that a single dose of psilocybin induced long-term genetic and functional changes in neurons in the OFC, and excitatory and inhibitory neurons jointly reduced circuit activity of the brain region. Samples of OFC of the brain were dissected and analyzed with single-nucleus RNA-seq