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Inhibitory  GABA ergic interneurons create different brain activity patterns that correlate with behavioural states. In this characterizing study, we used single‐cell RNA‐Seq to analyse anatomically‐ and electrophysiologically identified hippocampal oriens‐lacunosum moleculare ( OLM ) interneurons.  OLM s express somatostatin (Sst), generate feedback inhibition and play important roles in theta oscillations and fear encoding. Although an anatomically‐ and biophysically homogenous population, OLMs presumably comprise of two functionally distinct types with different developmental origins, inferred from the expression pattern of serotonin type‐3a (5‐ HT 3a, or  Htr3a ) receptor subunit and 5‐ HT  excitability in a set of  OLM s. To broadly characterize  OLM  cells, we used the Sst‐Cre and the  BAC  transgenic Htr3a‐Cre mouse lines and separately analysed SstCre‐ OLM  and Htr3aCre‐ OLM  types. We found a surprisingly consistent expression of  Npy  in  OLM s, 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  OLM s may originate from multiple neurogenic zones. Together, we found that  OLM s constitute a highly homogenous transcriptomic population. Finally, our results revealed surprisingly infrequent expression of  Htr3a  in only ~10% of  OLM s and an apparently specific expression of the 5‐ HT 3b subunit‐coding gene  Htr3b  in Htr3aCre‐ OLM s, but not in SstCre‐ OLM s. 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.

Single‐cell RNA‐Seq characterization of anatomically identified OLM interneurons in different transgenic mouse lines