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“Dry cleaning” effect—research shows how mice, and people, work on autopilot

Yale Medicine Magazine, 2009 - Spring


By watching mice navigate a custom-designed swimming pool, Christopher Pittenger, M.D., Ph.D., assistant professor of psychiatry, has discovered an ongoing competition between one part of the brain devoted to active seeking and another part devoted to mindless cruising. These two sections of the brain, his research shows, can inhibit each other, depending on the task at hand or, in this case, at paw. The competition, which likely occurs in people as well, may explain why it can be so hard to alter set routines, and could explain the power of such unwanted habits as drug addiction or obsessive-compulsive behaviors.

Pittenger’s study found that two parallel learning and memory systems that reside in different parts of the brain can block each other’s functions. The striatum powers up when—as if on autopilot—we embark on a well-known route like driving to work. The hippocampus comes into play when we need to think about where we’re going, as when we’re looking for a new address or detouring for an errand. The study found that when one system is impaired, the other is enhanced: in mice, injuring the striatum made the animals worse at locating a visual target in a water maze, but better at more active hippocampus-based navigational skills, and vice versa.

This reciprocal inhibition may explain the difficulty many people have in breaking from an entrenched routine. “This is why I cannot, for the life of me, remember to drop off my dry cleaning on the way to work,” said Pittenger, whose findings were published in October in Proceedings of the National Academy of Sciences.

“When you have driven the same route many times and are doing it on autopilot, it can be really difficult to change. If I’m not paying enough attention right at that moment, if I am thinking about something else, I just sail right on by.”

On a more serious note, the findings may also help explain the behavioral peculiarities seen with some brain diseases. Alzheimer disease, for example, destroys hippocampal function. That may be why many people with this disease fall back on old behaviors, like repeatedly returning to a previous address, thinking it is still home. Other diseases, including obsessive-compulsive disorder (OCD) and Parkinson disease, involve striatal malfunction. Pittenger’s new results emphasize that this striatal malfunction is likely to lead to changes in the function of the hippocampus, too, which may either compensate for or exacerbate the symptoms of the disease.

Understanding the connections between memory systems may offer new ways to treat serious behavioral problems. “A lot of psychiatric diseases are characterized by recurrent, maladaptive patterns of thought or behavior,” says Pittenger, who is also director of the Yale Obsessive-Compulsive Disorder Research Clinic. “People with OCD or drug addiction just keep doing the same thing and can’t seem to stop, no matter how hard they try.”

Treatment for OCD often includes cognitive behavioral therapy, which works by engaging a more reflective thinking mode to try to control automatic behaviors. Pittenger speculates that the process may work by recruiting one brain region to overcome an excess in the other. If so, it might be possible to develop drugs to make cognitive therapy more effective by enhancing or balancing the activities of the striatum or hippocampus.

It’s quite a leap from mice paddling in a pool to human disease, Pittenger said, but learning how basic normal memory systems work in animals is an important first step.

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