AgRP Neurons Implicated in Hunger Pains and Food-Seeking Behavior

A study published today in Nature sheds new light on the complex interplay among the neurons that govern hunger, food-seeking behavior, and the learning of food-acquisition tasks.

Focusing on the AgRP hunger neurons—the subpopulation of neurons found in the brain's hypothalamus responsible for creating the sensation of hunger after periods of deprivation— study leader Bradford Lowell from Beth Israel Deaconess Medical Center (BIDMC) and colleagues used a BIDMC-developed mouse model to investigate the neurons' activity.

The team trained the engineered mice to recognize a food cue by associating a light with access to food. As they expected, they observed that fasting activated AgRP neurons, and food cues in the environment—via a network of neurons elsewhere in the brain—work to inhibit AgRP activity. But remarkably, when the team blocked off this network, it caused the mice to have great difficulty learning a task in which sensory cues related to food were used to guide acquisition of food.

From this, the researchers suggest that fasting or deprivation—known to activate the AgRP neurons and the feeling of hunger—causes an unpleasant, or aversive, feeling. When food cues in the environment inhibit AgRP activity, it also tamps down the aversive feeling, which in turn serves as a reward powerful enough to enhance learning.

"It's as if these rewarding, sensory cue-linked drops in unpleasant AgRP neuron activity push the mouse towards environmental cues and tasks associated with obtaining food," said Lowell. "An obvious implication of this idea is that it explains why dieting is so difficult—dieters are perpetually stuck with this aversive feeling. So, in short, it appears that we eat and drink because we've learned that this reduces the activity of these deprivation neurons, and hence the linked bad feelings."