Summary: Researchers identified a brain circuit in mice that drives them to seek food even when they are not hungry. The team focused on a specific population of GABAergic neurons in the periaqueductal gray (PAG) of the brainstem, showing that activating these cells prompts vigorous food-seeking and a strong preference for high-calorie, rewarding foods.
The study indicates that humans have comparable cells, raising the possibility that similar mechanisms could contribute to eating disorders. By increasing or decreasing the activity of these neurons in mice, researchers could respectively enhance or suppress food-seeking behavior, pointing toward potential targets for treatment of compulsive eating and some forms of anorexia.
Key Facts:
- Specific brain cells drive food-seeking: Stimulating vgat-expressing neurons in the lateral and ventrolateral PAG (l/vlPAG) caused mice to forage and pursue food even when not hungry, distinguishing the neural basis of craving from the homeostatic drive of hunger.
- Relevance to eating disorders: The presence of similar neurons in humans suggests that overactivity or underactivity in this circuit could alter the perceived reward from food, potentially contributing to compulsive overeating or diminished eating-related pleasure in conditions such as anorexia.
- Preference for high-calorie foods: When these PAG neurons were activated, mice showed a clear preference for fatty and sugary foods over healthier options, and were willing to accept negative consequences to obtain them, supporting a role for this circuit in cravings for highly rewarding food.
Source: UCLA
Overview
UCLA psychologists discovered that a small cluster of neurons in the PAG—a brainstem region historically linked to defensive behaviors like panic—can specifically promote food-seeking and foraging without producing hunger itself. These vgat-expressing cells appear to increase motivation to seek out and consume highly rewarding foods, such as fatty or sugary items, even after a meal.
Corresponding author Avishek Adhikari, a UCLA associate professor of psychology, notes that the PAG is an evolutionarily old and conserved structure, making it plausible that basic behaviors like foraging are mediated there. The finding emerged as the research group investigated how this PAG region contributes to fear and anxiety processing.
While broad activation of the PAG triggers strong defensive and panic responses, targeted stimulation of the vgat PAG neuron cluster produced a different effect: mice engaged in active foraging and feeding behaviors without showing altered fear responses. This distinction supported the view that these neurons specifically regulate motivational aspects of food seeking rather than defensive reactions.
Methods and behavioral effects
The researchers used viral vectors to express light-sensitive proteins selectively in vgat-expressing PAG neurons. A laser delivered light through a fiber-optic implant, activating the neurons, while a small head-mounted microscope recorded neural activity in freely moving mice. When the vgat PAG cells were activated, mice pursued live crickets and non-prey food items with renewed vigor, even if they were recently sated.
Activation also caused mice to follow moving objects that were not edible—such as ping-pong balls—without attempting to eat them, and to explore their environment more confidently. These behaviors indicate an increase in approach and investigation driven by wanting or craving, rather than by physiological hunger.
Behaviorally, sated mice with stimulated vgat PAG neurons were willing to tolerate foot shocks to obtain fatty foods, demonstrating compulsive-like consumption. In complementary experiments, suppressing the activity of these neurons reduced foraging behavior even when mice were hungry, showing that the circuit is both necessary and sufficient to drive food-seeking and consumption.
Implications
The findings suggest this PAG circuit can override normal hunger cues and influence what and when animals eat. Because humans possess similar vgat PAG neurons, dysregulation of this circuit might increase the rewarding value of food and promote compulsive eating, or, if underactive, reduce eating-related pleasure and contribute to restrictive eating. If further research confirms comparable mechanisms in people, these neurons and their pathways could become targets for therapeutic strategies aimed at certain eating disorders.
Funding: The research was supported by the National Institute of Mental Health, the Brain & Behavior Research Foundation, and the National Science Foundation.
About this hunger and neuroscience research news
Author: Holly Ober
Source: UCLA
Contact: Holly Ober – UCLA
Image: The image is credited to Neuroscience News
Original Research: Open access. “Control of feeding by a bottom-up midbrain-subthalamic pathway” by Avishek Adhikari, et al. Published in Nature Communications.
Abstract
Control of feeding by a bottom-up midbrain-subthalamic pathway
Exploratory foraging and the behaviors that lead to food consumption are essential but incompletely understood. GABAergic inputs to the lateral and ventrolateral periaqueductal gray (l/vlPAG) influence these behaviors. The study dissected the role of vgat-expressing GABAergic l/vlPAG neurons in exploration, foraging, and hunting.
The authors demonstrate that in mice, vgat l/vlPAG cells encode approach to food and consumption of both live prey and non-prey items. These neurons are both necessary and sufficient to induce food-seeking that leads to consumption. Activation produces exploratory foraging and compulsive eating without changing defensive behaviors. l/vlPAG vgat cells are bidirectionally connected with several feeding and exploration nodes, including the zona incerta, and the projection from l/vlPAG to zona incerta bidirectionally controls approach to food and subsequent consumption.
These results indicate that the PAG functions not only as a downstream target of top-down exploratory inputs but also as a bottom-up influence on foraging and feeding behaviors.