Stress leads to enhanced food intake and a shift in dietary choices towards more high-caloric and unhealthy food. While this serves an adaptive purpose to replenish energy stores after a physical challenge, in modern society where continuous psychological stressors are present and cheap unhealthy food easily accessible, this likely contributes to tthe current alarming situation regarding obesity levels, with severe consequences for our health. Moreover, people with an eating disorder, like binge-eating disorder, are vulnerable to the effects of stress on maintaining their pathology. What circuits are implicated in these disorders is poorly understood. Human and animal studies both point to a critical role of the prefrontal cortex in coordinating stress-induced food intake. The prefrontal cortex is a highly heterogenous structure sending coordinated neuronal output to many brain regions with opposing roles in food regulation. This indicates that these circuits are under tight regulation of local interneurons. However, how interneurons coordinate circuits for stress-induced feeding behaviour and which projection neurons in the prefrontal cortex are important for stress-eating, is not known. To investigate this, we use a mouse model with stress leading to enhanced intake of palatable food. In this project I use this model to understand how inhibitory interneurons shape output patterns of prefrontal cortical pyramidal neurons in a projection-specific manner to drive stress-induced food intake. We focus on communication between the cortex and the hypothalamus (a region with a prominent role in regulating food intake) This study yields important insight into the circuit mechanisms underlying stress effects on food intake. Studying how this phenomenon arises at the level of neuronal circuits may ultimately provide evidence-based targets for prevention strategies.
