Details

Autor(en) / 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

Titel

Interleukin-4 receptor signaling modulates neuronal network activity

Ist Teil von

• The Journal of experimental medicine, 2022-06, Vol.219 (6)

Ort / Verlag

United States: Rockefeller University Press

Erscheinungsjahr

2022

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• 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.