Integrated Parallel Pathways Provide For Fear and Unpleasant Memories

Integrated Parallel Pathways Provide For Fear and Unpleasant Memories ...

Our survival depends on our responses to threats. It's well-known that the amygdala is critical in regulating fear. However, little is known about how or whether signals from our five sense organs are processed before reaching the amygdala.

A research published in the journal Cell Reports has identified two distinct populations of neurons in the thalamus and the brainstem that are activated by threat signals from the senses. Both these populations express a protein called CGRP, which group threatening sensory signals into an integrated signal, label the unified signal negative, and send it to two non-overlapping regions of the amygdala.

The findings described in the article (A central alarm system that sends multi-sensory innate threat signals to the amygdala) may lead to new therapies for post-traumatic stress disorder (PTSD), hypersensitivity, autism, migraines, and fibromyalgia.

Sukjae Kang, PhD, is a postdoctoral fellow at the Salk Institute's Clayton Foundation Laboratories for Peptide Biology, and a senior author of the research. "We were surprised to discover that CGRP neurons are activated by negative sensory cues from all five senses, including sight, sound, smell, and touch," said the co-lead author of the study.

The present investigation shows that the amygdala, the brain's emotion center, receives threat signals from many different brain areas, including the brainstem (red) and the thalamus (green).

Shijia Liu, a graduate student at the Salk Institute, is the co-lead author of the paper. [Salk Institute]We concluded that CGRP neurons, found especially in subregions of the thalamus and the brainstem, may provide multisensory threat information to the amygdala. These may help form aversive memories.

To record CGRP neuronal activity, the researchers conducted miniscope single-cell calcium imaging experiments in freely moving mice fitted with optical fibers. They also used retrograde tracing using different fluorescent tags to determine the pathways that emerged after leaving the thalamus and brain.

Han explained that while mice were used in this investigation, humans also abundantly express CGRP, thus, the same brain regions may be implicated in threat perception-related psychiatric disorders.

Migraines may also activate these CGRP neurons in the thalamus and brainstem, according to a postdoctoral fellow. This research is possible to leverage this information to alleviate threat memories in PTSD or sensory hypersensitivity in autism.

The Hans team intends to investigate the role of abnormalities in CGRP signaling in the two parallel circuits during migraine, PTSD, and autism in future experiments.

You may also like: