Image credit: Gyeong Hee Pyeong (CC BY 4.0)
How animals decide to respond to threatening situations can be the difference between life and death. Most animals show different defensive behaviors depending on how severe the threat is. For example, if it is imminent, they may flee to escape. On the other hand, if a threat is less severe, they may freeze to avoid detection.
The brain uses its own ‘general alarm system’ to help recognize and respond to threats. This system is made up of nerve cells which detect potential threat signals, ‘analyze’ them, and relay information about them to other parts of the brain that trigger the appropriate response. In humans, imbalances in this response can lead to maladaptive defense responses, such as those seen in anxiety or post-traumatic stress disorders, where fear and avoidance responses are excessive in relation to the threat.
One population of nerve cells, known as CGRP neurons, can detect a wide range of signals, and are known to respond by triggering passive behavior, such as freezing. However, whether CGRP neurons also trigger active behaviors, such as fleeing, remained unclear. Therefore, Pyeon et al. set out to study how CGRP neurons influence both passive and active defensive behaviors in response to varying threat levels.
To create realistic ‘models’ of different threat intensities in the laboratory, Pyeon et al. used a predator-like robot programmed to chase mice at different speeds. The mice were genetically modified so that researchers could record the activity of CGRP neurons, as well as activate the neurons artificially using light.
Activating CGRP neurons in mice being chased at a slow speed led to fleeing responses comparable to those observed during a higher-speed chase. This suggests that enhancing the alarm signal by artificially activating CGRP neurons may have caused the mice to perceive the threat as more intense and to react as though the danger was greater than it actually was. In contrast, mice with their CGRP neurons artificially ‘switched off’ were very unlikely to flee or freeze regardless of the speed of the chase.
The findings reveal that CGRP neurons respond differently to varying threat levels and regulate both passive and active defensive behaviors. This highlights their important role in adapting defensive responses to the severity of the threat. Building on these insights, future studies could explore strategies to regulate CGRP neuron activity, potentially leading to therapeutic approaches to address conditions marked by exaggerated or insufficient threat responses.
