Persistent large-scale changes in alternative splicing in prefrontal cortical neuron types following psychedelic exposure

The goal of this project was to assess the cell-type specific transcriptomic changes induced by psychedelics in a rodent model. We used the RiboTag technique to isolate RNA from genetically-defined neuronal subtypes in the mouse prefrontal cortex. Conditional tagging of the ribosomal protein Rpl22 was done with Pvalb-Cre, Cux2-CreERT, and Rbp4-Cre for PV interneurons, L2/3 pyramidal neurons, and L5 pyramidal neurons respectively. We deep-sequenced (~100 million paired-end reads) the RNAs using Illumina platforms. We found cell-type specific gene expression and alternative splicing changes associated with psychedelics, providing a essential resource for understanding the various effects of psychedelics on cortical cell types and functions. We mapped ribosome-bound RNA after treatment with saline or psychedelics DOI or psilocybin in genetically-defined neurons of the mouse prefrontal cortex, with 4-5 replicates per cell type, per time point, and per treatment.