Scientists may have identified the neurons that light up fear – ScienceAlert

It is sometimes said that you can smell fear, when in fact the cues that generate fear are usually multi-sensory.

A fire, for example, has heat, smoke and smell to give it. An eagle flying overhead casts a shadow and creates a flapping sound as it soars.

It would be useful for survival if animals had a way to feed all this sensory information from sight, smell, touch, taste and hearing into a neural circuit that would trigger a part of the brain called the amygdala to initiate a fear response once determined. threshold has been reached.

However, the existence of this neural pathway has not yet been established. A new study has now provided strong evidence of two non-overlapping circuits working together to trigger fear in our brains.

The team of researchers in the study began with the suspicion that neurons that make use of a molecule called calcitonin gene-related peptide (CGRP) played an important role in the process, along with the ” “fear center” of the brain: the amygdala.

Testing their hypothesis in genetically engineered mice, they found two distinct populations of these CGRP neurons in the brainstem and thalamus that connected to the animal’s amygdala.

Human neurons also express CGRP, so it is possible that this circuit is involved in conditions such as migraines, PTSD and autism spectrum disorder.

A piece of brain anatomy. (Mark Garlick/Science Photo Library/Getty Images)

The researchers fitted the mice with a small calcium imaging device called a miniscope, which allows scientists to track the activity of CGRP neurons as the mouse moves freely and responds to its environment.

The mice then faced threat stimuli, including a small shock to the foot; a burst of sound imitating thunder; an expanding, rising disc that simulates the rapid approach of a bird overhead; a cotton top soaked in trimethylthiazoline, a component of fox dung that causes fear in rodents; and quinine solution, which has a bitter taste.

The scientists recorded the activity of 160 CGRP neurons, half of each of the two varieties: CGRPSPFp and CGRPPBel.

They found that most CGRP neurons increased their activity when the mouse was confronted with threatening sounds, tastes, smells, sensations and visual cues. Neurons did not respond as strongly to control stimuli.

“The brain pathway we discovered works like a central alarm system,” says Sung Han, a neurobiologist at the Salk Institute for Biological Studies in California.

“We were excited to find that CGRP neurons are activated by negative sensory signals from the five senses: sight, sound, taste, smell and touch.”

The researchers wanted to confirm that these CGRP neurons were necessary for multisensory threat perception. In other words, that other neurons did not trigger the same fear response.

In mice they silenced the CGRP neurons and ran the experiment again to see if the animals continued to show the same pattern of fear behavior in response to fearful stimuli.

The researchers found that mice that had these neurons silenced were significantly less likely to respond to an electric foot shock or loud sounds.

“These results indicate that CGRPSPFp and CGRPPBel Neurons are required to mediate behavioral responses to different sets of multisensory threats,” the researchers write in their paper.

The team also showed that these CGRP neurons were needed to form threat memories using a so-called Pavlovian learning experiment.

By converging all these threat signals into a single area of ​​the brain, it can help animals make decisions easier, the researchers conclude.

If this same CGRP neural circuit is found in humans, this research may inform treatments for medical conditions.

“We haven’t tested it yet, but migraines could also activate these CGRP neurons in the thalamus and brainstem,” says neuroscientist and co-author Sukjae Joshua Kang, also of the Salk Institute for Biological Studies.

“Drugs that block CGRP have been used to treat migraines, so I hope our study can be an anchor point for using these types of drugs to relieve threatening memories in PTSD or sensory hypersensitivity. in autism too.”

This article was published in Cell reports.

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