Functional specification of CCK plus interneurons by alternative isoforms of Kv4.3 auxiliary subunits

Olah, Viktor Janos [Oláh, Viktor János (Neurobiológia), author] Laboratory of Cellular Neuropharmacology; School of PhD Studies (SU); Lukacsovich, David; Winterer, Jochen; Arszovszki, Antonia [Arszovszki, Antónia (Neurobiológia), author] Laboratory of Cellular Neuropharmacology; Lorincz, Andrea [Lőrincz, Andrea (Neuroanatómia), author] Laboratory of Cellular Neurophysiology; Nusser, Zoltan [Nusser, Zoltán (Celluláris idegél...), author] Laboratory of Cellular Neurophysiology; Foldy, Csaba; Szabadics, Janos ✉ [Szabadics, János (Celluláris neurof...), author] Laboratory of Cellular Neuropharmacology

English Article (Journal Article) Scientific
Published: ELIFE 2050-084X 2050-084X 9 Paper: e58515 , 26 p. 2020
  • SJR Scopus - Biochemistry, Genetics and Molecular Biology (miscellaneous): D1
Identifiers
Fundings:
  • ERC-AdG(787157)
  • Wellcome Trust(WT, 087497)
  • NAP2.0(KTIA_13_NAP-A-I/5 Funding details: NAP2.0)
Subjects:
  • Biological sciences
CCK-expressing interneurons (CCK+INs) are crucial for controlling hippocampal activity. We found two firing phenotypes of CCK+INs in rat hippocampal CA3 area; either possessing a previously undetected membrane potential-dependent firing or regular firing phenotype, due to different low-voltage-activated potassium currents. These different excitability properties destine the two types for distinct functions, because the former is essentially silenced during realistic 8-15 Hz oscillations. By contrast, the general intrinsic excitability, morphology and gene-profiles of the two types were surprisingly similar. Even the expression of Kv4.3 channels were comparable, despite evidences showing that Kv4.3-mediated currents underlie the distinct firing properties. Instead, the firing phenotypes were correlated with the presence of distinct isoforms of Kv4 auxiliary subunits (KChIP1 vs. KChIP4e and DPP6S). Our results reveal the underlying mechanisms of two previously unknown types of CCK+INs and demonstrate that alternative splicing of few genes, which may be viewed as a minor change in the cells' whole transcriptome, can determine cell-type identity.
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2024-07-18 01:37