MIT Institute Professor Ann Graybiel, PhD ’71, first identified this brain circuit in 2015 and showed that disrupting it using optogenetics, a technique that allows neurons to be controlled with light, could steer animals toward choosing higher-risk options.

In the new study, published in Cell, Graybiel and colleagues trained normal rats and mice to choose between a maze arm that exposed them to bright light (high-risk) and led to a reward of full-strength chocolate milk (high-payoff) or one involving dimmer light (low-risk) and weaker chocolate milk (low-payoff). The animals started out choosing each side about half the time, but as the researchers gradually increased the concentration of the chocolate milk found in the dimmer side, they began choosing that side more frequently.

When animals that had been exposed to a short period of stress every day for two weeks were put in the same situation, however, they continued to choose the bright light/better milk side even as the chocolate concentration increased on the dimmer side. The researchers believe that when animals are chronically stressed, circuit dynamics shift and a set of neurons involved in this type of decision-making becomes overexcited.

“Somehow this prior exposure to chronic stress controls the integration of good and bad,” Graybiel says. “It’s as though the animals had lost their ability to balance excitation and inhibition in order to settle on reasonable behavior.”

Once this shift occurs, it remains in effect for months, the researchers found. However, they were able to restore normal decision-making in the stressed mice by optogenetically manipulating a set of neurons in the circuit. This suggests that the circuit could be susceptible to manipulation that would restore normal behavior in human patients.