Mouse cortex PV interneuron transcriptome changes assessed with FACS-assisted bulk RNA-seq

To investigate the novel link between CP-AMPARs and excitability, we assessed global PV interneuron transcriptome changes with FICSR-seq (Fixation-Capture Single Cell RNA Recovery-seq) on forebrain PV interneurons. FACS-assisted PV interneuron bulk RNA-seq of PV-Cre;lsl-eGFP-GluA2 mice and PV-Cre;lsl-eGFP controls showed no expression changes in 278 out of 279 genes comprising the major classes of ion channels and excitatory/inhibitory synapse proteins. This lack of expression changes suggests a post-transcriptional regulation of intrinsic and extrinsic (synaptic) excitability. The exception was GluA2 mRNA, which was expressed ~2 fold compared to control PV interneurons, in agreement with protein measurements. GluA1, although downregulated at protein level, was unchanged at the mRNA level. These transcriptomic results suggest that the substantial changes in PV interneuron excitability after CP-AMPAR removal are not supported by changes in gene expression but likely reflect post-transcriptional regulation.