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

Eur J Neurosci. 2019 Dec;50(11):3750-3771. doi: 10.1111/ejn.14549. Epub 2019 Sep 5.


Inhibitory GABAergic 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. 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 presumably comprise of two functionally distinct types with 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 analysed 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.

Keywords: Htr3a; OLM; interneuron; neurexin; single-cell RNA-Seq.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Hippocampus / chemistry
  • Hippocampus / cytology*
  • Hippocampus / metabolism*
  • Interneurons / chemistry
  • Interneurons / metabolism*
  • Male
  • Mice
  • Mice, Transgenic
  • Organ Culture Techniques
  • RNA-Seq / methods*
  • Receptors, Serotonin, 5-HT3 / biosynthesis
  • Receptors, Serotonin, 5-HT3 / genetics
  • Transcriptome / physiology


  • Receptors, Serotonin, 5-HT3