Visual Overview
Visual Abstract
Abstract
Learning and adaptation during sources of threat and safety are critical mechanisms for survival. The prelimbic (PL) and infralimbic (IL) subregions of the medial prefrontal cortex (mPFC) have been broadly implicated in the processing of threat and safety. However, how these regions regulate threat and safety during naturalistic conditions involving thermal challenge still remains elusive. To examine this issue, we developed a novel paradigm in which adult mice learned that a particular zone that was identified with visuospatial cues was associated with either a noxious cold temperature (“threat zone”) or a pleasant warm temperature (“safety zone”). This led to the rapid development of avoidance behavior when the zone was paired with cold threat or approach behavior when the zone was paired with warm safety. During a long-term test without further thermal reinforcement, mice continued to exhibit robust avoidance or approach to the zone of interest, indicating that enduring spatial-based memories were formed to represent the thermal threat and thermal safety zones. Optogenetic experiments revealed that neural activity in PL and IL was not essential for establishing the memory for the threat zone. However, PL and IL activity bidirectionally regulated memory formation for the safety zone. While IL activity promoted safety memory during normal conditions, PL activity suppressed safety memory especially after a stress pretreatment. Therefore, a working model is proposed in which balanced activity between PL and IL is favorable for safety memory formation, whereas unbalanced activity between these brain regions is detrimental for safety memory after stress.
Footnotes
The authors declare no competing financial interests.
We thank Danny Hajali, Gianna Aleman, Daniel Arriaga, Bianca Moreno, and Savannah Lopez for technical assistance. We also thank Dr. Jose Rodriguez-Romaguera for insightful comments on an earlier version of the manuscript.
This work was supported by the UTSA College of Science and a UT-System Program for Science and Technology Acquisition and Retention (STARs). Support was also provided by the NIH grants R25EB027605 and T34GM145507.
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.