Project description
Unraveling the role of interneurons in brain circuits responsible for stress-related food intake
Emerging evidence underscores a crucial role for the prefrontal cortex (PFC) in coordinating stress-induced food intake. However, the PFC is a highly heterogeneous structure that sends neuronal output to many brain regions with opposing roles in food regulation. How this divergent output is coordinated is not known. The EU-funded CoMPOSE project proposes to investigate the mechanism by which interneurons orchestrate PFC output circuits during feeding behavior and how stress leads to adaptations in the activity patterns of these neurons to drive enhanced food intake. The project's results are of high socioeconomic importance, considering that modern life stress shifts dietary choices towards calorie-dense foods, and individuals with binge-eating disorder are particularly vulnerable to this. Moreover, the identification of evidence-based targets is central to the design of new prevention strategies against obesity.
Objective
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 leads to an alarming situation where many people overeat. As a consequence, obesity levels are rising with severe consequences for our health. Especially people with an eating disorder, like binge-eating disorder, are vulnerable to this situation. Human and animal studies both point to a critical role of the prefrontal cortex (PFC) 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 behavior is not known. In this project I aim to understand how Inhibitory interneurons shape output patterns of prefrontal cortical pyramidal neurons in a projection-specific manner to drive stress-induced food intake. To this aim I will use a combination of viral tracing techniques and in vivo electrophysiological recordings of identified PFC interneurons and pyramidal neurons in mice. Moreover I will use chemogenetic approaches to manipulate specific PFC pyramidal neural circuits to understand their role in stress eating responses. This will yield important insight into the circuit mechanisms underlying this maladaptive behavior. Studying how this phenomenon arises at the level of neuronal circuits will provide evidence-based targets for prevention strategies.
Fields of science
Programme(s)
Funding Scheme
MSCA-IF-EF-ST - Standard EFCoordinator
3584 CX Utrecht
Netherlands