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Switching Off a Specific Brain Region Can Alter Ingrained Habits in Rats

Science Update

Ingrained habits in rats can be quickly broken—and reestablished—by targeting and switching off a specific site in the brain’s prefrontal cortex using a technique known as optogenetics, according to an NIMH-funded study published November 13, 2012, in the Proceedings of the National Academy of Sciences (PNAS).


rat in a maze

Studies have established that the prefrontal region of the brain is associated with habit formation and expression. It is also linked to emotion regulation and to regions in the brain that are associated with behavioral flexibility, which counteracts habit.

Kyle Smith Ph.D., Ann Graybiel Ph.D., of the Massachusetts Institute of Technology, and colleagues, trained rats to run a T-shaped maze. At the decision point, the rats were cued to turn to either one side, where chocolate milk awaited them as a reward, or to the other side, where the reward was sugar water. Eventually, running the maze and responding to each cue correctly became a habit, and the rats continued to do so even after the rewards were removed.

The researchers then returned the rewards but paired the chocolate milk with exposure to lithium chloride, which causes nausea. Once the rats realized the milk made them ill, they declined to drink it. However, they continued to run the maze and turn toward the chocolate milk side of the maze when cued, indicating that running in that direction when prompted had become a nearly automatic behavior.

Results of the Study

To determine whether the habit could be broken, the researchers then applied a technique known as optogenetics—in which a laser light is delivered to brain cells through optical fibers—to see if they could manipulate a specific region of the rats’ prefrontal cortex known as the infralimbic (IL) cortex. When the laser was turned on and the IL cortex was disrupted, the rats nearly instantaneously stopped running habitually toward the chocolate milk reward. Instead, they appeared to act more thoughtfully, running toward the other side, where the untainted sugar water awaited.

Once the rats were broken of the habit of running automatically to the chocolate milk side, they began to develop a habit of always running to the other side, even when they were cued to run toward the chocolate milk, and even after the untainted chocolate milk was returned. But when the IL region was again disrupted optogenetically, the rats returned to their original habit of running to the chocolate milk side when cued to do so.


Control of a small part of the prefrontal cortex can change whether or not habits are expressed. An old habit can be blocked abruptly, and a new habit can override it. But if the new habit is then blocked, the old habit returns, thus lending credence to the notion that old habits die hard.

In addition, the fact that habitual behavior can be altered if IL activity is disturbed suggests that the circuitry in this region of the brain is coordinating on some level with other brain regions that directly access circuits involved in behavioral flexibility, as well as addictive behaviors.

What’s Next

Although the optogenetic technique is too invasive to use in humans, it does have implications for potentially disrupting destructive habits. Targeting this specific region of the brain could lead to better ways of controlling addiction disorders or mental disorders in which habitual behaviors are out of balance, such as obsessive compulsive disorder.


Smith K, Virkud A, Deisseroth K, Graybiel A. Reversible online control of habitual behavior by optogenetic perturbation of media prefrontal cortex. PNAS. Nov 13, 2012. 109(46):18932-18937.