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4h ago

Immune Signal IL-1β Triggers Brain Circuit That Drives Social Withdrawal in Mice

Researchers trace a causal pathway from IL-1R1-positive dorsal raphe neurons to the intermediate lateral septum that mediates sickness-induced isolation.

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Overview

  • Among 21 cytokines tested, only interleukin-1 beta reproduced the social withdrawal seen after LPS-induced immune activation.
  • Activating IL-1R1-expressing neurons in the dorsal raphe nucleus was sufficient to suppress social behavior, while inhibiting them or deleting IL-1R1 prevented withdrawal without reducing lethargy.
  • Optogenetic stimulation of the dorsal raphe connection to the intermediate lateral septum alone triggered the same withdrawal behavior.
  • The circuit engaged during a real bacterial challenge with salmonella, supporting its role in natural infection.
  • Published in Cell, the study led by MIT’s Gloria Choi and Harvard’s Jun Huh with lead author Liu Yang outlines a mouse mechanism and flags open questions about serotonin and human relevance.