School of Medicine

Neuroscientists Discover the Brain Circuity for Persistence

Why do some people give up easily and others do not? A common leadership ability among extraordinary achievers—such as CEOs, inventors, astronauts, best-selling authors, successful artists and musicians, popular comedians, media stars, trail-blazing entrepreneurs, ace pilots, Nobel prize winning scientists, and professional athletes—is persistence and motivation—the ability to go the extra mile and not give up easily.

Is there a biological basis to why some are able to persist more than others? A new scientific study published on July 25, 2019, in Cell identifies the molecular underpinnings and brain circuity that constrain motivation when the effort increases to obtain a reward—a new discovery that is the first step towards developing novel treatments for those suffering from addiction, depression, eating disorders, psychiatric disorders, and other mental health conditions.

In a four-year study, researchers from the University of Washington (UW) School of Medicine, and the Washington University School of Medicine, in collaboration with colleagues at other institutions, uncovered what actually happens inside the animal brain at the point of giving up.

“One of the key aspects of this work is that we identified a previously unknown neuromodulator system that regulates another neuromodulator dopamine,” said Michael Bruchas, the study’s senior author and professor at the University of Washington School of Medicine, and principal faculty member at UW’s Center for Neurobiology of Addiction, Pain, and Emotion. “This suggests even more complex relationships with neuropeptide modulators in the brain and monoamine systems like the dopamine and serotonin system.”

To conduct the study, researchers used Pavlovian conditioning on mice. In behavior psychology, Pavlovian conditioning, named after the 1904 Nobel laureate Ivan Petrovich Pavlov, is the method of using a powerful biological reward such as tasty food paired with a predefined stimulus like an image or sound. In this study, the researchers conditioned mice who were food restricted to receive the reward of sugar water when they complete the task of poking their nose in a designated port.

Other techniques the researchers used in the study include optogenetics, chemogenetics, and photometry. The scientists recorded the activity of the brain cells as the mice performed the task. They discovered that a group of brain cells located near the ventral tegmental area (VTA), called the nociceptin neurons, become very active prior to the mice giving up. The nociceptin neurons activity increased as the mice decreased their efforts to obtain the reward of sugar water.

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