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Both sides now: Brain reward molecule helps learning to avoid unpleasant experience, too

University of Pennsylvania School of Medicine

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IMAGE: Dopamine innervation into the hippocampus. Green denotes general catecholamine -- a general name for dopamine -- innervation of the CA1 region of the hippocampus. Yellows denotes dopamine nerve endings in... view more

Credit: Credit: John Dani, Ph.D., Perelman School of Medicine, University of Pennsylvania

PHILADELPHIA - The brain chemical dopamine regulates how mice learn to avoid a disagreeable encounter, according to new research from the Perelman School of Medicine at the University of Pennsylvania. "We know that dopamine reinforces 'rewarding' behaviors, but to our surprise, we have now shown that situations that animals learn to avoid are also regulated by dopamine," said senior author John Dani, PhD, chair of the department of Neuroscience. The team's findings are published this month in Cell Reports.

Special neurons in the brain send out a burst of dopamine in both negative and positive situations. However, the exact way in which dopamine neurons are wired and connected to the brain center called the hippocampus remains controversial among neuroscientists. Knowing exactly how the neurotransmitter dopamine shapes memory and behavior in association with an event or the surrounding environment is important to better understand such conditions as post-traumatic stress syndrome.

"We showed in mice that a special circuit in the hippocampus has flexibility in combining with environmental input to shape behavior during an experiment in which the mice learn to avoid an unpleasant experience," Dani said. "This is the first time that we have been able to show, as proof of principle, that the dopamine circuitry is also involved in learning to avoid aversive situations. "

Prevailing Questions

In previous animal experiments, when mice experience an unexpected reward, for example discovering a tube in which they can obtain a sugar-water treat, a burst of dopamine is emitted in the brain. The debate among neuroscientists centers on whether the neurotransmitter only shapes behavior when an animal is receiving a positive reward or if the neurotransmitter is also involved in shaping the way an animal learns how to avoid an uncomfortable situation.

The team found that if the mice encounter an negative stimuli, a subgroup of neurons fires and releases dopamine in conjunction with the aversive environmental input. They also showed that when the dopamine signal to the hippocampus is chemically blocked in the mice, it prevents them from learning to avoid the negative stimulus. However, if the dopamine signal is chemically boosted in the mice, they remember to avoid the aversive event longer.

"The bottom line of our study is that dopamine plays a role in both conditions, and that dopamine enables mice to learn and remember to avoid the negative situation, in this case avoid a light foot shock in one room of a two-room enclosure."

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Co-authors include postdoctoral fellows Kechun Yang and Theo Tsetsenis, both from Penn, and John Broussard, Baylor University.

This work was supported by the National Institutes of Health (NS21229, DA09411, DA021194, MH067119, DA017173).

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania(founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $5.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report -- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.

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