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The Journal of Neuroscience, October 29, 2008, 28(44):11124-11130; doi:10.1523/JNEUROSCI.2820-08.2008

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Behavioral/Systems/Cognitive
Double Dissociation of the Effects of Medial and Orbital Prefrontal Cortical Lesions on Attentional and Affective Shifts in Mice

Gregory B. Bissonette,^1,3 * Gabriela J. Martins,^1,3 * Theresa M. Franz,¹ Elizabeth S. Harper,¹ Geoffrey Schoenbaum,^1,2,3 and Elizabeth M. Powell^1,2,3

Departments of ¹Anatomy and Neurobiology and ²Psychiatry, and ³Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201

Correspondence should be addressed to Dr. Elizabeth M. Powell, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, HSF II S251, 20 Penn Street, Baltimore, MD 21201. Email: epowe001{at}umaryland.edu or Email: epowel{at}gmail.com

Many neuropsychiatric diseases are associated with cognitive rigidity linked to prefrontal dysfunction. For example, schizophrenia and Parkinson's disease are associated with performance deficits on the Wisconsin Card Sorting Test, which evaluates attentional set shifting. Although the genetic underpinnings of these disorders can be reproduced in mice, there are few models for testing the functional consequences. Here, we demonstrate that an analog of the Wisconsin Card Sorting Test, developed in marmosets and recently adapted to rats, is a behavioral model of prefrontal function in mice. Systematic analysis demonstrated that formation of the attentional set in mice is dependent on the number of problem sets. We found that mice, like rats and primates, exhibit both affective and attentional sets, and these functions are disrupted by neurotoxic damage to orbitofrontal and medial prefrontal cortical areas, respectively. These data are identical to studies in rats and similar to the deficits reported after prefrontal damage in a comparable task in marmosets. These results provide a behavioral model to assess prefrontal function in mice.

Key words: executive function; cognitive flexibility; reversal learning; set shifting; Wisconsin Card Sorting Test; behavior

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Received June 19, 2008; revised Sept. 8, 2008; accepted Sept. 12, 2008.

Correspondence should be addressed to Dr. Elizabeth M. Powell, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, HSF II S251, 20 Penn Street, Baltimore, MD 21201. Email: epowe001{at}umaryland.edu or Email: epowel{at}gmail.com

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