Published June 3, 2014
Zhen Yan, PhD, professor of physiology and biophysics, has received $1.6 million to continue her study of human dopamine D4 receptor variants — a type of neurotransmitter receptor in the brain’s prefrontal cortex.
She aims to identify molecular targets and key signaling components involved in the different functions of these variants. Her work could pave the way for future research leading to new treatments for diseases associated with abnormalities in dopamine function.
Human D4 receptor variants have been highly associated with attention deficit hyperactivity disorder (ADHD), autistic traits and problems like drug abuse, risk taking and novelty-seeking behaviors, Yan explains.
“Some have been associated with deficiencies in executive control processes in conditions like schizophrenia and ADHD,” she notes.
In the prefrontal cortex — the brain region critical for cognition and emotion — “human D4 receptor variants may differentially regulate high-level executive functions such as working memory, attention, decision making, emotional control and personality.”
Yan aims to better understand the molecular and physiological basis of the variants — also known as polymorphisms — of the receptors.
She and her team hypothesize that the human D4 receptor variants differentially regulate activities in the prefrontal cortex by interacting with different proteins and activating distinct signaling pathways, a process that contributes to their roles in mental health and disorders.
She will use a combination of approaches to test the functional role of human D4 receptor polymorphisms in prefrontal cortex circuits.
Yan’s five-year grant from the National Institute on Drug Abuse is the second renewal of funding for the project since 2004.
In previous studies, Yan increased understanding about both the function and dysfunction of dopamine D4 receptors.
She showed that the dopamine D4 receptor plays an important role in regulating excitatory and inhibitory signals in the prefrontal cortex.