Deep within the brainstem is a structure no bigger than a grain of rice, the locus coeruleus. The LC is often referred to as the “blue spot” because of a distinct blue pigment produced from its inner synthesis reactions.
Despite its microscopic size —2 millimiters x 12 millimeters — the LC is central to memory and the production of norepinephrine, a neural signaling molecule essential to the response to stress.
The LC nerve cells are capable of changing the brain's level of alertness and arousal, attention, learning and memory. The LC transmits signals that mark a piece of information as meaningful so that it can be recalled. This complex also helps us react to external stimuli, reevaluate our surroundings and plan new courses of action.
Despite the fact that the LC is frequently dismissed by standard biology textbooks, research associate Elizabeth Riley, psychology, a member of the Affect and Cognition Lab, explains that this region is quite ancient, dating all the way back in the family tree of life.
“When we think about cognition and human brain diseases, we often think about parts of the brain that are newer or more specialized in humans —that's not the case here,” Riley said.
Another leading explanation for the underappreciation of the LC is that it is difficult to study the phenotypes produced by specific lesions in the brain stem because any damage often proves fatal.
“It took a long time to understand how these tiny brain stem structures that are so ancient and deep in the brain are actually having a profound effect on our behavior," said Riley.
Indeed, researchers have only recently begun to appreciate how critical and vulnerable this tiny structure is. The LC system's correlation to Alzheimer’s is associated with the complex’s initial deterioration and worsening as the disease progresses. Alzheimer’s is a brain disorder with loss of memory, thinking, and reasoning that interferes with daily life.
The LC is among the first regions of the brain to fall victim to Alzheimer’s-like changes at 20 or 30 years of age. Furthermore, death of nerve cells in the LC can be used to track the severity and progression of the onset of Alzheimer's.
However, this tiny region is difficult to image. Structural MRI techniques allow researchers to capture a picture of the places in the brain full of neuromelanin, a metabolism waste product of the synthesis of norepinephrine. This neuromelanin builds up throughout an individual’s lifespan, from the generation of dopamine and norepinephrine.
“We don’t quite fully understand yet how this technique works. We can take a picture of the two brain regions that have neuromelanin in them, which includes the locus coeruleus,” Riley said.
However, there has been the rise of promising interventions to help maintain LC function with aging. Vagus nerve stimulation is a technique that delivers an electrical current through the skin at points where the vagus nerve, which transmits signals for involuntary movement, lies closest to the skin. Its name comes from the Latin word “vagus,” meaning “wanderer,” reflecting the nerve’s extensive reach throughout the torso of the body.
“The vagus nerve takes all the information from your gut and your heart, and all kinds of other places, and it brings it up to your brain. On the way up to the brain, we can deliver stimulation,” Riley said. “Stimulating the vagus nerve is one step away from stimulating the locus coeruleus. So we can modulate how the LC is working with vagus nerve stimulation.”
This might reveal that this form of stimulation might improve the LC’s functioning in older adults and improve symptoms of Alzheimer’s disease.
Furthermore, Riley points to music’s “magical power” in neurodegenerative disorders, where familiar songs can help patients “wake up.” She wonders whether the LC might underlie this intriguing effect.
Music modulates human emotions and the LC is a central player in shaping our affective state. Heightened LC activity, with its surge in norepinephrine production, often accompanies stress. Relaxation, on the other hand, reflects a strong parasympathetic tone.
Acting like a “thermostat,” the LC integrates signals from across the brain to adjust norepinephrine levels. When music allows us to relax, part of that response is expressed through the LC.
Moving forward, Riley hopes to integrate music into her future research, exploring whether musical engagement itself helps preserve LC function as we age.
