MAIN PROBLEM AND IMPORTANCE:
Stress can drive an increase in appetite for high caloric foods, rich in fat and sugar. This is particularly problematic in those individuals vulnerable to develop obesity or eating disorders characterized by binge eating (voracious intake of a large amount of food in a short period of time). The way in which stress affects food choices and food intake is via its action on the brain. However, the precise pathways (i.e. connections between brain regions) that are specifically affected by stress, the mechanisms through which this occurs, and the specific consequences of such changes for feeding behavior, remain unclear. Obesity and eating disorders with a binge eating component are pressing societal issues. A better understanding of the role of stress in these conditions, and in particular an understanding of how stress dysregulates the brain to contribute to these conditions, can be important anchor points for future evidence-based treatments.
OVERALL OBJECTIVES:
Our goal was to study which brain circuits are important in stress eating. We focused on the prefrontal cortex (PFC), a region known across species for its importance in decision making, impulse control, but also formulating behavior strategies. It's also a very stress-sensitive region, and it's a region implicated in eating disorders and obesity. Interestingly, this PFC makes a very strong connection with another brain region called the Lateral hypothalamic area (LHA). That region is very well known for its role in food intake. Connection in this case means that there are neurons with their cell bodies in the PFC, that send their projection outputs (axons) to the LHA, allowing them to control the activity of the neurons there. Within the LHA you have neurons that are more involved in driving appetite for tasty foods, and also neurons that are more involved in braking appetite. We set out to test our hypothesis that stress would change the communication between PFC and LHA in such a way that the LHA 'drive for food' neurons would become more active and/or that the LHA 'brake for food' neurons would become less active, such that enhanced appetite for food and even binge eating would follow. We sought to address this in a mouse model, because mice allow for much more detailed brain circuit investigations. Moreover, in mice we can not only measure brain activity, we can also manipulate it. By doing so we can get much closer to drawing conclusions about the importance of a region activity for a behavior (like eating). Mouse brains, while not the same as human brains, nevertheless share many similarities in brain anatomy (same brain regions exist, and many of the connections between the regions are the same, also the basic properties of how neurons communicate with each other has many similarities between mice and humans). Finally, mice can also increase their food intake after stress. In part because these stress-driven food intake responses likely have an evolutionary 'useful' function, depending on the environmental conditions.
CONCLUSIONS:
We used measurement techniques to show that during stress (a social confrontation) results in immediate reactivity in the PFC neurons that communicate with the LHA. Interestingly, in the aftermath of this initial response there is a resetting of the strength of connection between the PFC and distinct types of LHA neurons. Indeed, the stimulatory message that is sent from the PFC to those LHA neurons that can increase food intake is strengthened by stress. Instead, the stimulatory message that is sent from PFC neurons to other types of LHA neurons, which can brake food intake when stimulated, is weakened. As a result of this cocktail of effects, the PFC control over the LHA shifts more towards promoting the intake of food after stress. In accordance we show that if the PFC-LHA pathway is inhibited, this has an interesting effect. Namely, it reduces the excess intake of fat that the mice would normally have when stressed, bringing their food intake to the normal levels of a non-stressed mouse. In conclusion, the PFC-LHA pathway, which remains little studied, is more complex than previously thought. As we showed that this pathway has multiple branches (different types of LHA neurons receive PFC input). Also, stress causes changes (called plasticity) in these distinct PFC-LHA branches, in a manner that creates more drive for food and less brake on intake. Those changes play an important role in mediating the effect of stress on the bingeing of tasty high-caloric food.
