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J Neurophysiol (December 7, 2005). doi:10.1152/jn.01052.2005
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Submitted on October 6, 2005
Accepted on December 4, 2005

ENCODING CHANGES IN ORBITOFRONTAL CORTEX IN REVERSAL-IMPAIRED AGED RATS

Geoffrey Schoenbaum1*, Barry Setlow2, Michael P. Saddoris3, and Michela Gallagher3

1 Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA; Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA
2 Psychology, Texas A&M University, College Station, TX, USA
3 Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD, USA

* To whom correspondence should be addressed. E-mail: schoenbg{at}schoenbaumlab.org.

Previous work in rats and primates has shown that normal aging can be associated with a decline in cognitive flexibility mediated by prefrontal circuits. For example, aged rats are impaired in rapid reversal learning, which in young rats depends critically on the orbitofrontal cortex. To assess whether aging-related reversal impairments reflect orbitofrontal dysfunction, we identified aged rats with reversal learning deficits and then recorded single-units as these rats, along with unimpaired aged cohorts and young control rats, learned and reversed a series of odor discrimination problems. We found that the flexibility of neural correlates in orbitofrontal cortex was markedly diminished in aged rats characterized as reversal-impaired in initial training. In particular, while many cue-selective neurons in young and aged-unimpaired rats reversed odor preference when the odor-outcome associations were reversed, cue-selective neurons in reversal-impaired aged rats did not. In addition, outcome-expectant neurons in aged-impaired rats failed to become active during cue sampling after learning. These altered features of neural encoding could provide a basis for cognitive inflexibility associated with normal aging.




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