Human cortical interneurons show local co-expression of GLP1R and insulin mRNA

This study investigated whether specific human cortical interneuron subtypes locally express glucagon-like peptide-1 receptor (GLP1R) and insulin (INS), hypothesizing this molecular feature might be relevant for intracortical metabolic signaling. Researchers analyzed single layer 1 GABAergic interneurons microdissected from human cortical tissue using laser capture microdissection. Transcriptomic subtype identification was performed using digital PCR preamplification of LAMP5, SV2C, and PRSS12 markers. GLP1R and INS mRNA copy numbers were quantified using single-cell digital PCR, and spatial expression patterns were validated using RNAscope Hi-Plex in situ hybridization. Results showed neurogliaform cells (LAMP5+, SV2C+, PRSS12–) and rosehip cells (LAMP5+, SV2C+, PRSS12+) exhibited significantly higher GLP1R and INS expression than other LAMP5 interneurons. Specifically, GLP1R mRNA was found in 44 out of 72 neurogliaform cells and 18 out of 36 rosehip cells. INS mRNA was detected in 29 out of 72 neurogliaform cells and 11 out of 36 rosehip cells. No INS expression was detected in other LAMP5 interneurons. Co-expression analysis revealed a significant statistical dependency between GLP1R and INS expression, with a mutual information value of 0.244 (p<0.001). The study demonstrates local co-expression of GLP1R and INS in specific human cortical interneuron populations, suggesting a potential molecular substrate for intracortical metabolic signaling.