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


Winterer, Jochen; Lukacsovich, David; Que, Lin; Sartori, Andrea M; Luo, Wenshu; Földy, Csaba (2019). Single‐cell RNA‐Seq characterization of anatomically identified OLM interneurons in different transgenic mouse lines. European Journal of Neuroscience, 50(11):3750-3771.

Abstract

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.

Abstract

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Scopus Subject Areas:Life Sciences > General Neuroscience
Uncontrolled Keywords:General Neuroscience
Language:English
Date:1 December 2019
Deposited On:16 Jan 2020 08:54
Last Modified:29 Jul 2020 12:40
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0953-816X
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1111/ejn.14549
PubMed ID:31420995
Project Information:
  • : FunderSNSF
  • : Grant ID31003A_170085
  • : Project TitlePhysiological and molecular definition of PV interneuron synapses in the hippocampus
  • : FunderSNSF
  • : Grant IDCRETP3_166815
  • : Project TitleTrans-synaptic signaling in GABAergic synapses (ERC-2014-StG)

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