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Updated: Jun 26, 2026
11:19
Correlating Gene-specific DNA Methylation Changes with Expression and Transcriptional Activity of Astrocytic KCNJ10 Kir4.1
Published on: September 26, 2015
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Functional KCC2 expression marks an evolutionarily conserved population of early-maturing interneurons in the
Rakenduvadhana Szrinivasan1, Kalevi Trontti2, Rémi Mathieu3,4
1Neuroscience Centre, HiLife, University of Helsinki, Helsinki, Finland. rakenduvadhana.srinivasan@helsinki.fi.
Nature Communications
|December 9, 2025
Summary
Early-maturing cortical interneurons (INs) expressing KCC2 show GABAergic responses at birth, unlike other neurons. This discovery reveals heterogeneous GABAergic maturation in the developing brain.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- GABAergic transmission maturation is crucial for cortical circuit development.
- The temporal pattern of GABAergic response maturation in cortical interneurons (INs) is not well understood.
- KCC2 transporter expression is linked to GABAergic response maturation.
Purpose of the Study:
- To investigate the maturation timeline of GABAergic responses in cortical interneurons (INs).
- To identify and characterize early-maturing IN subpopulations.
- To explore the role of KCC2 in early IN maturation and its evolutionary conservation.
Main Methods:
- Utilized a high-resolution mouse cortical development atlas.
- Employed single-cell RNA sequencing and spatial transcriptomics.
- Performed differential gene expression (DGE) analysis and electrophysiological recordings.
Main Results:
- Identified early-maturing INs expressing KCC2 at embryonic stages with hyperpolarizing GABAergic responses at birth.
- These INs exhibit precocious excitability, synaptic integration, and dendritic complexity.
- Found these INs are predominantly in layer 5, express somatostatin, and show upregulated synaptogenic genes.
- Demonstrated evolutionary conservation of these early-maturing INs in humans.
Conclusions:
- GABAergic functional maturation is heterogeneous within IN subpopulations.
- KCC2 serves as a marker for early-maturing cortical INs.
- Early-maturing INs play a significant role in establishing early cortical circuit function.
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