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. Overall design: Samples of OFC of the brain were dissected and analyzed with single-nucleus RNA-seq