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Hanuscheck, Nicholas [Author]; Thalman, Carine [Author]; Domingues, Micaela [Author]; Schmaul, Samantha [Author]; Muthuraman, Muthuraman [Author]; Hetsch, Florian [Author]; Ecker, Manuela [Author]; Endle, Heiko [Author]; Oshaghi, Mohammadsaleh [Author]; Martino, Gianvito [Author]; Kuhlmann, Tanja [Author]; Bozek, Katarzyna [Author]; van Beers, Tim [Author]; Bittner, Stefan [Author]; von Engelhardt, Jakob [Author]; Vogt, Johannes [Author]; Vogelaar, Christina Francisca [Author]; Zipp, Frauke [Author]

Interleukin-4 receptor signaling modulates neuronal network activity

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  • Media type: E-Article
  • Title: Interleukin-4 receptor signaling modulates neuronal network activity
  • Contributor: Hanuscheck, Nicholas [Author]; Thalman, Carine [Author]; Domingues, Micaela [Author]; Schmaul, Samantha [Author]; Muthuraman, Muthuraman [Author]; Hetsch, Florian [Author]; Ecker, Manuela [Author]; Endle, Heiko [Author]; Oshaghi, Mohammadsaleh [Author]; Martino, Gianvito [Author]; Kuhlmann, Tanja [Author]; Bozek, Katarzyna [Author]; van Beers, Tim [Author]; Bittner, Stefan [Author]; von Engelhardt, Jakob [Author]; Vogt, Johannes [Author]; Vogelaar, Christina Francisca [Author]; Zipp, Frauke [Author]
  • Published: Augsburg University Publication Server (OPUS), 2022
  • Language: English
  • DOI: https://doi.org/10.1084/jem.20211887
  • Origination:
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  • Description: Evidence is emerging that immune responses not only play a part in the central nervous system (CNS) in diseases but may also be relevant for healthy conditions. We discovered a major role for the interleukin-4 (IL-4)/IL-4 receptor alpha (IL-4Rα) signaling pathway in synaptic processes, as indicated by transcriptome analysis in IL-4Rα–deficient mice and human neurons with/without IL-4 treatment. Moreover, IL-4Rα is expressed presynaptically, and locally available IL-4 regulates synaptic transmission. We found reduced synaptic vesicle pools, altered postsynaptic currents, and a higher excitatory drive in cortical networks of IL-4Rα–deficient neurons. Acute effects of IL-4 treatment on postsynaptic currents in wild-type neurons were mediated via PKCγ signaling release and led to increased inhibitory activity supporting the findings in IL-4Rα–deficient neurons. In fact, the deficiency of IL-4Rα resulted in increased network activity in vivo, accompanied by altered exploration and anxiety-related learning behavior; general learning and memory was unchanged. In conclusion, neuronal IL-4Rα and its presynaptic prevalence appear relevant for maintaining homeostasis of CNS synaptic function.
  • Access State: Open Access