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

View ORCID ProfileViktor János Oláh, David Lukacsovich, Jochen Winterer, Andrea Lőrincz, View ORCID ProfileZoltan Nusser, Csaba Földy, View ORCID ProfileJános Szabadics
doi: https://doi.org/10.1101/683755
Viktor János Oláh
1Laboratory of Cellular Neuropharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
2János Szentágothai School of Neurosciences, Semmelweis University, Budapest, Hungary
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  • ORCID record for Viktor János Oláh
David Lukacsovich
3Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Natural Sciences, University of Zurich, Zurich, Switzerland
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Jochen Winterer
3Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Natural Sciences, University of Zurich, Zurich, Switzerland
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Andrea Lőrincz
4Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
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Zoltan Nusser
4Laboratory of Cellular Neurophysiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
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Csaba Földy
3Laboratory of Neural Connectivity, Brain Research Institute, Faculties of Medicine and Natural Sciences, University of Zurich, Zurich, Switzerland
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János Szabadics
1Laboratory of Cellular Neuropharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
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  • ORCID record for János Szabadics
  • For correspondence: szabadics.janos@koki.mta.hu
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Abstract

CCK-expressing interneurons (CCK+INs) are crucial for controlling hippocampal activity. We found two firing phenotypes of CCK+INs in rat 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. The general 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 event in the cells’ whole transcriptome, can underlie distinct cell-type identity.

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Posted June 27, 2019.
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Functional specification of CCK+ interneurons by alternative isoforms of Kv4.3 auxiliary subunits
Viktor János Oláh, David Lukacsovich, Jochen Winterer, Andrea Lőrincz, Zoltan Nusser, Csaba Földy, János Szabadics
bioRxiv 683755; doi: https://doi.org/10.1101/683755
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Functional specification of CCK+ interneurons by alternative isoforms of Kv4.3 auxiliary subunits
Viktor János Oláh, David Lukacsovich, Jochen Winterer, Andrea Lőrincz, Zoltan Nusser, Csaba Földy, János Szabadics
bioRxiv 683755; doi: https://doi.org/10.1101/683755

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