It is sometimes said that you can smell fear, while the signals that generate the feeling afraid for no reason are often multisensory.
Fire, for example, has heat, smoke, and odor to get rid of. An eagle flying in the sky casts its shadows and creates a faint sound as it turns over. It would be beneficial for survival if the animals had a way of feeding all that sensory information of sight, smell, touch, taste and hearing into a single neural circuit that triggers a part of the brain called the amygdala to initiate a fear response.
However, the existence of such a neural pathway has not yet been proven. A new study has now provided strong evidence that two non-overlapping circuits work together to instill feeling afraid in our brains.
The team of researchers behind the study began with suspicions that neurons using a molecule called calcitonin gene-related peptide (CGRP) played a powerful role in this process, along with the brain’s “fear center” – the amygdala.
Testing their hypothesis in genetically modified mice, they found two distinct groups of CGRP neurons in the brain stem and thalamus connected to the animal’s amygdala.

Human neurons also express CGRP, so it is possible that this circuit is implicated in conditions such as migraines, post-traumatic stress disorder and autism spectrum disorder.
The researchers fitted the mice with a small calcium imaging device called a miniscope, which allows the scientists to track the activity of CGRP neurons while the mouse roams freely and responds to its environment.
The mice then encountered threatening stimuli, including a small shock to their foot; A burst of sound simulating an explosion of thunder; Expanded disc looming simulates the rapid approach of a bird over the head; a piece of cotton dipped in trimethylthiazolin, a component of fox excrement that provokes fear in rodents; And a solution of quinine, and its taste is bitter.

The scientists recorded the activity of 160 CGRP neurons, half of each of the two classes: CGRPSPFp and CGRPPBel.
They found that most CGRP neurons increased in activity when the rat experienced threatening sounds, tastes, smells, sensations and visual cues. The neurons did not respond with the same force to the control stimuli.
“The brain pathway we discovered works like a central alarm system,” says Song Han, a neuroscientist at the Salk Institute for Biological Studies in California. “We were excited to discover that CGRP neurons are activated by passive sensory signals from all five senses — sight, sound, taste, smell, and touch. “.
The researchers wanted to confirm that these CGRP neurons were required for multisensory threat perception. In other words, the other neurons were not eliciting the same fear response.
In mice, they silenced CGRP neurons and ran the experiment again to see if the animals continued to show the same pattern of fear behavior in response to the feared stimuli.
The researchers found that mice that had these neurons silenced were less likely to respond to electric foot shocks or loud sounds.
“These findings indicate that CGRPSPFp and CGRPPBel neurons are required to mediate behavioral responses to different sets of multisensory threats,” the researchers wrote in their paper.
