Dopamine, often called the “pleasure” chemical, is a neurotransmitter linked to a myriad of motivating behaviors, including pair bonding, sexual behavior, decision-making, and drug addiction. Because of its involvement with rewards, many have argued that dopamine receptors, particularly the D1 variety in the prefrontal cortex, should also be involved in feeding regulation. Yet just how the prefrontal cortex may be mediating feeding behavior remained unclear.
To examine the role of D1-type dopamine receptor–expressing neurons in feeding, Benjamin Land, a post-doctoral fellow in psychiatry at Yale University School of Medicine, and his colleagues in Ralph DiLeone’s laboratory turned to optogenetics.
“Optogenetics gives us really fine control over [neuron] firing—as well as cell-type specific control over firing. That allowed us very nice spatial and temporal control over specific cell types, so we could see how these changes in the cells were modifying behavior,” said Land.
Since food intake was known to increase activity in medial prefrontal cortex D1–expressing neurons, the group used light to stimulate those cells in transgenic mice, which resulted in increased feeding. And as you might expect, when the researchers inhibited the activity of D1-expressing cells, the animals ate less.
By modulating cell activity, the group was also able to identify the circuit responsible for feeding behavior. When Land’s team mapped the prefrontal D1–expressing neuron projections, they expected to see them operating through the nucleus accumbens, a part of the basal ganglia that is critical to reward processing and also involved in addiction. What they found instead were projections to the basolateral amygdala, identifying a new top-down circuit of interest.
“We were a bit surprised, to be honest, to find this new circuit. We thought prefrontal cortical stimulation might inhibit food intake. Instead, we found the opposite, with food intake operating in a D1 fashion through the basolateral amygdala,” said Land. “And you can actually stimulate the nerve terminals in the basolateral amygdala and recapitulate the feeding phenotypes we saw when we did the cell photostimulation in the prefrontal cortex, with stimulation there increasing feeding, too.”
As a next step, Land would like to map where the basolateral amygdala cells project and gain a better understanding of this newly discovered circuit. And with the looming obesity epidemic, he concedes that medial prefrontal D1–expressing cells may be a plausible pharmacological target to help modulate feeding behavior. Since the prefrontal cortex has been implicated, however, Land believes there may be equal therapeutic value in top-down awareness and cognitive control.
“It’s possible that we could one day use things like cognitive behavioral therapy, where you can give compulsive eaters or people who have trouble controlling their weight feedback that helps them learn how to control their cravings based on how their body is responding to food,” he said. “The fact that prefrontal cortex is involved may mean that ‘training’ your brain could work, too.”