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Transcriptomic Correlates of State Modulation in GABAergic Interneurons: A Cross-Species Analysis.

Joram Keijser1,2, Loreen Hertäg3, Henning Sprekeler3,4

  • 1Modelling of Cognitive Processes, Technical University of Berlin, 10587 Berlin, Germany keijser@tu-berlin.de joramkeijser@gmail.com.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|September 19, 2024
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Researchers explored how brain cell gene expression relates to behavioral states across species. They found significant differences in gene expression patterns between species, impacting how brain circuits function.

Keywords:
cell typesevolutioninhibitionsingle-cell RNA-sequencing

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Area of Science:

  • Neuroscience
  • Genomics
  • Comparative Biology

Background:

  • GABAergic inhibitory interneurons exhibit diverse subtypes with distinct properties.
  • In mouse visual cortex, interneuron state modulation correlates with gene expression, predictable by the first principal component (PC).

Purpose of the Study:

  • To investigate if the link between transcriptome and state-dependent processing in interneurons is conserved across species.
  • To analyze transcriptomic differences in forebrain cell types across mammals, birds, and reptiles.

Main Methods:

  • Analysis of seven single-cell and single-nucleus RNA sequencing datasets from mouse, human, songbird, and turtle.
  • Comparative analysis of transcriptomic principal components (PCs) and cell-type abundance.
  • Examination of cholinergic receptor expression and circuit modeling.

Main Results:

  • Transcriptomic PCs showed significant dissimilarities between species, increasing with evolutionary distance.
  • Differences arose from gene expression divergence within homologous cell types and variations in cell-type abundance.
  • Several cholinergic receptors, linked to mouse interneuron state modulation, were differentially expressed across species.

Conclusions:

  • The relationship between transcriptome and state-dependent processing is not fully conserved across species.
  • Evolutionary divergence in gene expression and cell-type composition underlies species-specific functional differences.
  • Differential expression of cholinergic receptors may contribute to functional variations in brain states across species.