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Advanced Science· 2026Q1

A Molecularly Defined Midbrain Circuit Mechanism for Sound‐Driven Defensive Behavior and Anxiety

Jie Cao, Xingxing Lai, Lifang Huo, Zhouyuan Zheng et al.

Short summary

Researchers identified Cerebellin-2-expressing (Cbln2+) neurons in the inferior colliculus shell (ICx) as key detectors of threatening sounds, essential for triggering defensive responses like escape, autonomic arousal, and fear memory.

AI-generated from the title and abstract; the full text is not read.

Key points

  • Cbln2+ neurons in the ICx act as specific detectors for threatening sounds.
  • Activation of Cbln2+ ICx neurons triggers escape behavior, autonomic arousal, and fear memory.
  • These neurons project to the dPAG, mediating sound-driven defensive and anxiety-like behaviors.
  • A midbrain circuit centered on the ICx regulates innate defense and anxiety via a subcortical pathway.

AI-generated from the title and abstract; the full text is not read.

Abstract

ABSTRACT The innate defense behaviors in response to threatening sounds play a fundamental role in survival. However, the neural circuits that detect threat‐relevant auditory cues and transform them into defensive behaviors remain poorly defined. Here, we identified Cerebellin‐2‐expressing (Cbln2+) neurons work as threatening sound detector in the inferior colliculus shell region (ICx) that were essential for the induction of sound‐driven defensive responses. Cbln2+ ICx neurons specifically responded to threatening sound in a graded manner, and their activation induces escape behavior, autonomic arousal, and fear memory formation. Moreover, this neural subtype provoked sound‐driven defensive and anxiety‐like behaviors through their projection to the dorsal periaqueductal gray (dPAG). Our findings reveal a molecularly defined midbrain circuit that regulates sound‐evoked innate defense and anxiety‐like states primarily through an ICx‐centered subcortical pathway.

The authors' abstract, as published at the source. Advanced Science, 2026 · DOI ↗

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Field: Endocrine and Autonomic Systems

Endocrine and Autonomic SystemsNeuroscience