Finding has implications for alcoholism and other patterns of addictive behavior.

Research  from the National Institutes of Health has identified neural circuits in mice  that are involved in the ability to learn and alter behaviors. The findings  help to explain the brain processes that govern choice and the ability to adapt  behavior based on the end results.

Researchers  think this might provide insight into patterns of compulsive behavior such as  alcoholism and other addictions.

“Much  remains to be understood about exactly how the brain strikes the balance  between learning a behavioral response that is consistently rewarded, versus  retaining the flexibility to switch to a new, better response,” said Kenneth R.  Warren, Ph.D., acting director of the National Institute on Alcohol Abuse and  Alcoholism. “These findings give new insight into the process and how it can go  awry.”

The  study, published online in Nature Neuroscience, indicates that specific  circuits in the forebrain play a critical role in choice and adaptive learning.

Like  other addictions, alcoholism is a disease in which voluntary control of  behavior progressively diminishes and unwanted actions eventually become  compulsive. It is thought that the normal brain processes involved in  completing everyday activities become redirected toward finding and abusing  alcohol.

The  research, conducted by investigators from NIAAA, with support from the National  Institute of Mental Health and the University of Cambridge, England, used a  variety of approaches to study choice.

Researchers  used a simple choice task in which mice viewed images on a computer touchscreen  and learned to touch a specific image with their nose to get a food  reward. Using various techniques to visualize and record neural activity,  researchers found that as the mice learned to consistently make a choice, the brain’s  dorsal striatum was activated. The dorsal striatum is thought to play an  important role in motivation, decision-making, and reward.

Conversely,  when the mice later had to shift to a new choice to receive a reward, the  dorsal striatum quieted while regions in the prefrontal  cortex, an area involved in decision-making and complex cognitive processes,  became active.

Building  upon these findings, the authors next deleted or pharmacologically blocked a  component of nerve cells which normally binds the neurochemical glutamate  (specifically, the GluN2B subunit of the NMDA receptor) within two different  areas of the brain, the striatum and the frontal cortex. Previous studies have  shown that GluN2B plays a role in memory, spatial reference, and attention.  Researchers found that making dorsal striatal GluN2B inactive markedly slowed  learning, while shutting down GluN2B in the prefrontal cortex made the mice  less able to relearn the touchscreen reward task after the reward image was  changed.

“These  data add to what we understand about the neural control of behavioral  flexibility and striatal learning by identifying GluN2B as a critical molecular  substrate to both processes,” said the study’s senior author, Andrew Holmes,  Ph.D., Laboratory Chief and Principal Investigator of the NIAAA Laboratory of  Behavioral and Genomic Neuroscience.

“This  is particularly intriguing for future studies because NMDA receptors are a  major target for alcohol and contribute to important features of alcoholism,  such as withdrawal.  These new findings suggest that GluN2B in  corticostriatal circuits may also play a key role in driving the transition  from controlled drinking to compulsive abuse that characterizes alcoholism.”

The National  Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of  Health, is the primary U.S. agency for conducting and supporting research on  the causes, consequences, prevention, and treatment of alcohol abuse,  alcoholism, and alcohol problems. NIAAA also disseminates research findings to  general, professional, and academic audiences. Additional alcohol research  information and publications are available at http://www.niaaa.nih.gov.

About the National Institutes of Health (NIH): NIH, the  nation's medical research agency, includes 27 Institutes and Centers and  is a component of the U.S. Department of Health and Human Services. NIH is  the primary federal agency conducting and supporting basic, clinical, and  translational medical research, and is investigating the causes,  treatments, and cures for both common and rare diseases. For more information  about NIH and its programs, visit http://www.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Reference:  GluN2B in corticostriatal circuits governs choice learning and choice shifting. Brigman JL, Daut R, Wright T, Gunduz-Cinar O, Graybeal C, Davis MI, Jiang Z, Saksida LM, Jinde S, Pease M, Bussey TJ, Lovinger DM, Nakazawa K, Holmes A. Nature Neuroscience. 2013 July 7. [Epub ahead of print]

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