UC Riverside has received a $2 million grant from the National Institute of Aging to study how the brain’s main norepinephrine production center regulates perception and memory in older adults. 

The results could improve noninvasive diagnoses and treatments for dementias associated with old age or Parkinson’s disease. The project will be led by bioengineering professor Xiaoping Hu and psychology professor Aaron Seitz.

The locus coeruleus is a region of the brain involved with physiological responses to stress and fear. It is the primary producer in the brain of norepinephrine, a hormone that activates the body’s “fight or flight” response to frightening or stressful situations by increasing heart rate, releasing glucose into the bloodstream, and increasing blood flow to the muscles.  

In the brain, norepinephrine acts as a neurotransmitter, passing messages between neurons to increase alertness and reaction time, and affect mood and ability to concentrate. There is substantial evidence that the locus coeruleus circuit plays a central role in cognitive processes. Neuronal loss in the locus coeruleus is known to occur in neurodegenerative disorders such as Alzheimer’s disease and related dementias and Parkinson’s disease dementia. 

Scientists think healthy locus coeruleus neurons preserve cognitive abilities during normal aging, but few studies have examined differences between individuals to establish a baseline. The locus coeruleus is small and difficult to image, so most research to date has used pupil dilation as a surrogate measure of locus coeruleus activity.

Hu and Seitz, along with UC Riverside psychology colleagues Illana Bennett and Weiwei Zhang, and Megan Peters at UC Irvine, have pioneered advanced neuroimaging methods to image the locus coeruleus. 

They will conduct detailed psychophysical and magnetic resonance imaging studies of older adults to understand how locus coeruleus structure and function regulates behavior and how this, in turn, is mediated by activity in other brain regions known to be involved in perception and memory. Their efforts will allow them to use computational approaches to define individual differences in the way locus coeruleus circuit integrity relates to different patterns of cognitive performance across tasks.

The team hopes their work can help explain how dysfunctional modulatory circuits may generate cognitive declines or be implicated in normal aging and age-related disorders such as Alzheimer’s and related disorders. The results have the potential to support noninvasive methods for diagnosing pathologies associated with locus coeruleus decline and developing new treatments.

^{Header photo: Artyom Kabajev on  Unsplash}