Study of neural circuit mechanism underlying visual threat learning

Abstract

Vision is the most important sensations in many species including humans. Through the vision, animals can avoid potential threat. Also, they associate neutral stimuli with visual threat to learn approach and attack of predators. Despite of the importance of visual threat learning, there has been rare studies for elucidating neural circuit mechanisms underlying visual threat learning. It is due to absence of proper behavioral test models in animals. Thus, this study established new behavioral model for visual threat learning in mice. In this model, the mice form auditory and contextual fear memory through the looming visual threat. By using the visual threat learning model, this study revealed that CGRP+ neurons in SPFp and PBN regions are necessary for processing the visual threat information. The two regions have been known as ascending pain pathways. Thus, the participation of these regions in processing visual threat information implies that SPFp and PBN might have central roles in mediating multi-modal sensory threats. Furthermore, this study verified the distinct role of CGRP$^{SPFp}$ and CGRP$^{PBN}$ neurons. The CGRP$^{SPFp}$ neurons are necessary in regulating immediate defensive behaviors against visual threat, while the CGRP$^{PBN}$ neurons mediate visual threat learning and learned freezing behaviors. In addition, we elucidate the SC is the upstream visual pathway that convey the visual threat information to the SPFp and PBN. By using retrograde tracing and optogenetic terminal inhibition method, this study discovered that non-overlapped subpopulations of SC neurons have convey functional inputs to the SPFp and PBN respectively. Another interesting discovery is that the pAIC-to-PBN pathway is also necessary in visual threat learning. It suggests that the PBN might be a central hub evaluating danger levels for threat learning by integrating comprehensive information from various brain areas. The present study reveals that CGRP$^{SPFp}$ and CGRP$^{PBN}$ neurons, which have been known as pain pathway, play essential roles in processing visual threat information. Moreover, it is demonstrated that the SPFp and PBN have distinguished functional role in immediate defensive behaviors and visual threat learning. Finally, the functional upstream pathways including SC-to-SPFp, SC-to-PBN, and pAIC-to-PBN were discovered in the study. This study is expected to significantly contribute to the understanding of the neural circuitry underlying visual threat learning, previously unexplored.