Know that the Brain translates Danger Stimuli into Fear?

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Know that the Brain translates Danger Stimuli into Fear?

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A molecular route has been discovered by researchers at the Salk Institute that integrates potentially threatening sights, sounds, and odours into a single message: Be scared. A molecule known as CGRP is responsible for enabling neurons in two separate regions of the brain to integrate potentially harmful sensory inputs into a coherent signal, label it as negative, and then transfer it to the amygdala, which converts the signal into fear.

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The results of the study were published in the journal Cell Reports. These findings might lead to the development of novel treatments for fear-related disorders such as post-traumatic stress disorder (PTSD) or hypersensitivity disorders such as autism, migraines, and fibromyalgia.

Know that the Brain translates Danger Stimuli into Fear
Know that the Brain translates Danger Stimuli into Fear?

According to the senior author, Sung Han, an assistant professor at the Clayton Foundation Laboratories for Peptide Biology at the Salk Institute for Biological Studies, the brain route that they found functions similarly to a central warning system. “We were ecstatic to make the discovery that the CGRP neurons are triggered by unfavourable sensory inputs originating from any of the five senses: sight, hearing, taste, smell, or touch. Insights into the treatment of fear-related disorders may be gained by the discovery of novel danger pathways.”

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The majority of hazards that come from the outside world include many senses, such as the heat, smoke, and scent that come from a wildfire. Previous studies have shown that distinct neural pathways independently transmit visual, auditory, and haptic signals of danger to a variety of brain regions. It would be helpful to one’s survival if there was a single route that integrated all of these inputs, but no one has ever uncovered such a pathway before.

Previous studies demonstrated that the amygdala, which is responsible for the initiation of behavioural responses and the formation of fear memories in response to environmental and emotional stimuli, receives significant input from brain regions that are loaded with a neuropeptide known to be associated with aversion. This chemical is called CGRP (calcitonin gene-related peptide).

According to Shijia Liu, a graduate student in the Han lab, who is also a co-first author on the study, “based on these two pools of research, we proposed that CGRP neurons, found especially in subregions of the thalamus and the brainstem, relay multisensory threat information to the amygdala. “It’s possible that these circuits are responsible for both the formation of appropriate behavioural responses and painful memories of threat stimuli.”

The group put its theories to the test by carrying out a number of experiments. Researchers were able to identify which sensory modalities were engaged with which groups of neurons because they monitored the activity of CGRP neurons using single-cell calcium imaging while simultaneously providing mice with multimodal danger signals. Using a variety of fluorescent proteins of varying colours, they were able to detect the direction that the signals travelled after leaving the thalamus and the brainstem. In addition to that, they carried out behavioural tests to evaluate the subjects’ memories and levels of terror.

Their results indicate that two separate populations of CGRP neurons, one in the thalamus and one in the brainstem, project to nonoverlapping sections of the amygdala, constituting two unique circuits. One of these populations is located in the thalamus, while the other is located in the brainstem. Both populations are able to decipher potentially dangerous sights, sounds, smells, tastes, and touches via the use of communication with local brain networks. In the end, scientists found out that both circuits are required for the formation of unpleasant memories, which are the kinds of memories that advise you to “Stay away.”

“While mice were employed in this research, the same brain areas also abundantly express CGRP in people,” says Han, holder of the Pioneer Fund Developmental Chair. “While mice were used in this study, the same brain regions also abundantly express CGRP in humans.” “This hints that the circuits revealed here could also be implicated in threat perception-related mental illness,” the authors write. The scientists want to investigate how CGRP signalling in these circuits affects disorders that include errors in the processing of multisensory inputs. Some examples of these disorders include migraines, PTSD, and autism spectrum disorder.

According to Sukjae Joshua Kang, a postdoctoral scholar in the Han lab, who is also a co-first author on the study, “We haven’t tested it yet, but migraines could also activate these CGRP neurons in the thalamus and brainstem.” However, this hypothesis has not been tested.
“Drugs that inhibit CGRP have been used to treat migraines; thus, I’m expecting that our research may serve as an anchor to apply this sort of medicine in easing threat memories in PTSD, as well as sensory hypersensitivity in autism.”

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