“You can’t teach an old dog new tricks.” New research indicates that this saying is true for rats and, with the animal model in place, it may lead to more insight about learning and memory in humans. A study from the University of Maryland School of Medicine and Johns Hopkins University has zeroed in on the particular region of the prefrontal cortex in the brain that is responsible for impaired processing and has found an abnormal neural firing pattern there. The findings are published in the March 2006 issue of the Journal of Neurophysiology, which is published by the American Physiological Society.
The research, supported by a Mentored Scientist Award from the National Institute of Aging, involved young and elderly rats. The rats learned that specific odors piped into an enclosed chamber predicted either a reward of water laced with sucrose or a punishment of water laced with bitter tasting quinine. “After the rats solved the initial problem, we reversed the meaning of the two odor cues, so the rats had to shift their behavior based on this new information,” says Geoffrey Schoenbaum, M.D., Ph.D., an assistant professor of anatomy and neurobiology at the University of Maryland School of Medicine, who served as principal investigator on the study. “So the odor predictive of the earlier reward becomes predictive of quinine and vice versa. Young rats learned these reversals rather quickly, but a subset of older animals was particularly impaired at acquiring them.”
According to Dr. Schoenbaum, elderly rats that couldn’t adjust their behavior after reversal of the odor cues had abnormal neural firing patterns in the orbitofrontal cortex, which is a part of the pre-frontal cortex that is particularly important for flexible decision making. “The neurons in the orbitofrontal cortex in older rats were inflexible in the way they encoded the associations between the odors and the outcomes, essentially firing in a way that reflected the old association after reversal,” he says. “These data provide a piece of the puzzle as to why some elderly rats, and perhaps people, have trouble changing their behavior or learning new ‘tricks.’”
“Such animal models, which have validity for what we see in humans, can be used to identify specific circuits and molecules that might be potential therapeutic targets to improve learning and memory and people,” says Dr. Schoenbaum.
Animal testing was conducted at Johns Hopkins University under Dr. Schoenbaum’s award and a Program Project Award to Michela Gallagher, Ph.D., the Krieger-Eisenhower Chair of the Department of Psychological and Brain Sciences at Johns Hopkins.
Related research is currently ongoing in Dr. Schoenbaum’s lab to investigate what other brain processes might be impacted in “reversal-impaired” elderly rats and to examine why some rats exhibit normal or even enhanced processing in the orbitofrontal cortex as they age.
“This work provides insight into why it becomes more difficult to change your behavior as you get older,” says Dr. Schoenbaum. “By exploring this phenomenon in rats, we gain a better understanding of how human cognitive function changes with age and it may ultimately be possible to use this model to test ways to change or even reverse that decline. For example, it may be possible to prevent aging-related cognitive decline by something as simple as dietary changes, mental or even physical exercise. Or we might be able to identify pharmaceutical approaches to prevent the loss of cognitive flexibility. Having an animal model that reproduces what we see in human aging provides an alternative approach to answering these critical questions.”
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