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

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.