Scientists may have identified neurons that generate fear: ScienceAlert

It is sometimes said that you can smell fear, when in fact the cues that generate fear are often multisensory.

Fire, for example, has heat, smoke, and smell to give it away. An eagle flying overhead casts a shadow and makes 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 single neural circuit that triggers a part of the brain called the amygdala to initiate a fear response once a threshold is set has been reached.

Yet the existence of such a neural pathway has not yet been established. A new study has now provided compelling evidence for two, non-overlapping circuits that work together to instill fear in our brains.

The team of researchers behind the study began with suspicions that neurons that use a molecule called calcitonin gene-related peptide (CGRP) play a strong role in the process, along with the brain’s “fear center,” the amygdala.

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

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

Fragment of the anatomy of the brain. (Mark Garlick/Science Photo Library/Getty Images)

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

Mice were then presented with threatening stimuli, including a small shock to their leg; a burst of sound imitating thunder; an expanding, looming disk simulating the rapid approach of a bird overhead; cotton tip soaked in trimethylthiazoline, a component of fox feces causes fear in rodents; and a solution of quinine, 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 encountered 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 Research in California.

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

The researchers wanted to confirm that these CGRP neurons are necessary for multisensory threat perception. In other words, that other neurons do not produce 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 fearful behavior in response to fearful stimuli.

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

“These results show that CGRPSPFp and CGRPPBel neurons are required to mediate behavioral responses to diverse sets of multisensory threats,” the researchers wrote in their paper.

The team also demonstrated that these CGRP neurons are necessary for forming threat memories using a so-called Pavlovian learning experiment.

By bringing all these threat signals together in one area of ​​the brain, it could help the animals make decisions easier, the researchers concluded.

If this same CGRP neural circuit is found in humans, then this research could provide information for the treatment of medical conditions.

“We haven’t tested it yet, but migraine may 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 Research.

“Drugs that block CGRP have been used to treat migraines, so I hope that our study can be a support for using this kind of drug to relieve threat memories in PTSD or sensory hypersensitivity in autism as well. “

This article was published in Cell reports.

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