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

• Published in: PLoS biology 2019-08, Vol.17 (8), p.e3000417-e3000417
• Main Authors: Wang, Haitao, Chen, Jiahui, Xu, Xiaotong, Sun, Wen-Jian, Chen, Xi, Zhao, Fei, Luo, Min-Hua, Liu, Chunhua, Guo, Yiping, Xie, Wen, Zhong, Hui, Bai, Tongjian, Tian, Yanghua, Mao, Yu, Ye, Chonghuan, Tao, Wenjuan, Li, Jie, Farzinpour, Zahra, Li, Juan, Zhou, Jiang-Ning, Wang, Kai, He, Jufang, Chen, Lin, Zhang, Zhi
• Format: Article
• Language: English
• Subjects: Acoustics; Analysis; Animal behavior; Animal defenses; Animals; Auditory cortex; Auditory Cortex - metabolism; Auditory Cortex - physiology; Auditory Perception - physiology; Behavior; Behavior, Animal - physiology; Biology; Biology and Life Sciences; Chemistry; Cortex (auditory); Defense Mechanisms; Defensive behavior; Escape behavior; Escape Reaction - physiology; Excitatory Amino Acids - physiology; Funding; GABAergic Neurons - physiology; Glutamatergic transmission; Heat treating; Hospitals; Laboratories; Male; Medicine and Health Sciences; Memory; Mental health; Mice; Mice, Inbred C57BL; Neural circuitry; Neural Pathways - physiology; Neurology; Neurons; Noise control; Optogenetics - methods; Periaqueductal Gray - metabolism; Periaqueductal Gray - physiology; Periaqueductal gray area; Physical sciences; Psychological aspects; Research and Analysis Methods; Social Sciences; Sound; Substrates; Threats; Trends; Virology; γ-Aminobutyric acid
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3000417

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.