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

Interleukin-4 receptor signaling modulates neuronal network activity

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  • Medientyp: E-Artikel
  • Titel: Interleukin-4 receptor signaling modulates neuronal network activity
  • Beteiligte: Hanuscheck, Nicholas; Thalman, Carine; Domingues, Micaela; Schmaul, Samantha; Muthuraman, Muthuraman; Hetsch, Florian; Ecker, Manuela; Endle, Heiko; Oshaghi, Mohammadsaleh; Martino, Gianvito; Kuhlmann, Tanja; Bozek, Katarzyna; van Beers, Tim; Bittner, Stefan; von Engelhardt, Jakob; Vogt, Johannes; Vogelaar, Christina Francisca; Zipp, Frauke
  • Erschienen: Rockefeller University Press, 2022
  • Erschienen in: Journal of Experimental Medicine, 219 (2022) 6
  • Sprache: Englisch
  • DOI: 10.1084/jem.20211887
  • ISSN: 0022-1007; 1540-9538
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: 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.
  • Zugangsstatus: Freier Zugang