Direct auditory cortical input to the lateral periaqueductal gray controls sound-driven defensive behavior

PLoS Biol. 2019 Aug 30;17(8):e3000417. doi: 10.1371/journal.pbio.3000417. eCollection 2019 Aug.


Threatening sounds can elicit a series of defensive behavioral reactions in animals for survival, but the underlying neural substrates are not fully understood. Here, we demonstrate a previously unexplored neural pathway in mice that projects directly from the auditory cortex (ACx) to the lateral periaqueductal gray (lPAG) and controls noise-evoked defensive behaviors. Electrophysiological recordings showed that the lPAG could be excited by a loud noise that induced an escape-like behavior. Trans-synaptic viral tracing showed that a great number of glutamatergic neurons, rather than GABAergic neurons, in the lPAG were directly innervated by those in layer V of the ACx. Activation of this pathway by optogenetic manipulations produced a behavior in mice that mimicked the noise-evoked escape, whereas inhibition of the pathway reduced this behavior. Therefore, our newly identified descending pathway is a novel neural substrate for noise-evoked escape and is involved in controlling the threat-related behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Auditory Cortex / metabolism
  • Auditory Cortex / physiology*
  • Auditory Perception / physiology
  • Behavior, Animal / physiology
  • Defense Mechanisms
  • Escape Reaction / physiology*
  • Excitatory Amino Acids / physiology
  • GABAergic Neurons / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways / physiology
  • Optogenetics / methods
  • Periaqueductal Gray / metabolism*
  • Periaqueductal Gray / physiology
  • Sound


  • Excitatory Amino Acids

Grants and funding

This work was supported by National Natural Science Foundation of China, (91732303 and 81870877 to ZZ, 81570915 to LC), the National Key Research and Development Program of China, (2016YFC1305900 to ZZ), and Anhui Provincial Natural Science Foundation, (1808085MH244 to HW). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.