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

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.