Researchers have identified a molecular pathway through which information from cues such as threatening sights, sounds and smells triggers the fear response.
According to a new peer-reviewed study published in the scientific journal Cell Reports on Tuesday, a molecule called CGRP allows neurons from two different areas in the brain to compile threatening stimuli into one signal, designate it as a negative signal and send the information to the amygdala, where it is translated into fear.
Previous research revealed that different brain pathways independently transmit sensory threat cues to multiple areas of the brain and that the amygdala receives large amounts of information from parts of the brain where the neuropeptide CGRP (calcitonin gene-related peptide), which is linked to aversion, is abundant.
The recent study, however, is the first to demonstrate that these cues can be transmitted via a single pathway.
In the study, the researchers used single-cell calcium imaging to record CGRP neuron activity and presented mice with threat cues in order to determine which sense involved which sets of neurons.
“We haven't tested it yet, but migraines might also activate these CGRP neurons in the thalamus and brainstem.”
Study co-first author Sukjae Joshua Kang
The researchers found the path of the signals using fluorescent proteins and determined the memory and fear levels of the mice by conducting behavioral tests.
The researchers found evidence that two different groups of CGRP neurons, one of which was located in the thalamus and one in the brainstem, projected to separate parts of the amygdala as two independent circuits, both of which communicated with networks in the brain to translate threatening stimuli.
The researchers also discovered that these circuits are essential to the process of forming aversive memories.\
What does this mean for future research?
The researchers aim to study how CGRP signaling in these circuits affects mental disorders related to multisensory processing, such as autism spectrum disorder, PTSD and migraines.
“We haven't tested it yet, but migraines might also activate these CGRP neurons in the thalamus and brainstem,” said co-first author Sukjae Joshua Kang. “Drugs that block CGRP have been used to treat migraines, so I’m hoping that our study can be an anchor to use this kind of drug in relieving threat memories in PTSD, or sensory hypersensitivity in autism, too.”