GSE124847
Single-cell RNAseq characterization of anatomically-identified OLM interneurons in different transgenic mouse lines
Inhibitory GABAergic interneurons create different brain activity patterns that correlate with behavioral states. In this characterizing study, we used single-cell RNAseq to analyze anatomically- and electrophysiologically-identified hippocampal oriens-lacunosum moleculare (OLM) interneurons. OLMs express somatostatin (Sst), generate feedback inhibition, and play important roles in theta oscillations and fear encoding. Although an anatomically- and biophysically-homogenous population, OLMs comprise two functionally distinct types with presumed different developmental origins, inferred from the expression pattern of serotonin type-3a (5-HT3a, or Htr3a) receptor subunit and 5-HT-excitability in a set of OLMs. To broadly characterize OLM cells, we used the Sst-Cre and the BAC-transgenic Htr3a-Cre mouse lines and separately analyzed SstCre-OLM and Htr3aCre-OLM types. We found a surprisingly consistent expression of Npy in OLMs, which was previously not associated with the identity of this type. Our analyses furthermore revealed uniform expression of developmental origin-related genes, including transcription factors and neurexin isoforms, without providing support for the current view that OLMs may originate from multiple neurogenic zones. Together, we found that OLMs constitute a highly homogenous transcriptomic population. Finally, our results revealed surprisingly infrequent expression of Htr3a in only ~10% of OLMs, and an apparently specific expression of the 5-HT3b subunit-coding gene Htr3b in Htr3aCre-OLMs, but not in SstCre-OLMs. However, additional in situ hybridization experiments suggested that the differential expression of Htr3b may represent an unexpected consequence arising from the design of the Htr3a-Cre BAC transgenic line. Overall design: mRNA profiles of 46 OLM cells (23 Sst line, 23 Htr3a line)