New Findings Challenge Dogma of How Dopamine-Releasing Neurons Communicate

Researchers at the University of Pittsburgh (Pitt) have uncovered the mechanism by which neurons keep up with the demands of repeatedly sending signals to other neurons. The new findings, made in fruit flies and mice, challenge the existing dogma about how neurons that release the chemical signal dopamine communicate, and may have important implications for many dopamine-related diseases, including schizophrenia, Parkinson's disease, and addiction. The research conducted at Pitt and Columbia University was published online on August 17, 2017 in Neuron. The article is titled “Neuronal Depolarization Drives Increased Dopamine Synaptic Vesicle Loading via VGLUT.” Neurons communicate with one another by releasing chemicals called neurotransmitters, such as dopamine and glutamate, into the small space between two neurons that is known as a synapse. Inside neurons, neurotransmitters awaiting release are housed in small sacs called synaptic vesicles. "Our findings demonstrate, for the first time, that neurons can change how much dopamine they release as a function of their overall activity. When this mechanism doesn't work properly, it could lead to profound effects on health," explained the study's senior author Zachary Freyberg, MD, PhD, who recently joined Pitt as an Assistant Professor of Psychiatry and Cell Biology. Dr. Freyberg initiated the research while at Columbia University. When the researchers triggered the dopamine neurons to fire, the neurons' vesicles began to release dopamine as expected. But then the team noticed something surprising: additional content was loaded into the vesicles before they had the opportunity to empty. Subsequent experiments showed that this activity-induced vesicle loading was due to an increase in acidity levels inside the vesicles.
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