Prefrontal control of hypothalamic feeding circuits: Balancing executive control of eating

Background
Binge-eating disorder and Anorexia Nervosa are physically debilitating eating disorders where advanced stages of the disease can result in a number of health-related consequences including a myriad of obesity-related diseases and extreme malnutrition, respectively. Early stages of these diseases are defined psychologically by a diminished or excessive control over the drive to eat that with time develop to psychiatric proportions. Circuits residing in the hypothalamus gauge the metabolic state of the organism, subsequently guiding food-seeking behaviour for maintaining energy homeostasis. These circuits respond to interoceptive energy-related cues irrespective of the psychological state of the individual. For normal food seeking behaviour to occur it is conceivable that these primary feeding circuits are under the tonic inhibitory influence of afferent structures that when over- or under-active can result in excessive or diminished control over the drive to eat. The prefrontal cortex is well known to act as the brain’s executive decision-maker, imposing cognitive control over choice behaviours for optimising behavioural outcomes for the animal’s well-being. Importantly, the medial PFC (mPFC) projects to the lateral hypothalamus (LH) revealing an anatomical substrate and thus candidate circuit for a direct top-down regulation of feeding behaviour. In a modern society where our drive to eat is mostly affected by factors that are independent of our nutritional needs understanding the brain circuits that impose control over our eating patterns will not only contribute to our understanding of eating disorders but also shed light on the mechanisms by which we choose to eat.

Aims and General Approach
It is thought that diminished or excessive control over the drive to eat in eating disorders results from under- or over-activation of prefrontal cortical (PFC) brain regions important in decision-making. To investigate the executive control over eating this project aims to link the underlying circuitry between the PFC and feeding-promoting circuits of the hypothalamus to eating. Novel circuit-mapping strategies will be implemented to determine the functional relation between the two structures. This information will set the groundwork for relating PFC and hypothalamic activity in a rodent eating disorder model that promotes under- or over-eating. By consisting of two phases, one where animals restrict their food intake, the other where they over-consume food, we will monitor and relate changes in PFC and hypothalamic activity across phases where animals exhibit distinct feeding patterns. Finally, using this model we will attempt to normalise feeding behaviour and hyperactivity by manipulating prefrontal inputs to the hypothalamus, thus determining a causal role for this circuit in influencing eating. In addition to linking executive circuits with feeding circuits this project aims to provide insight into the neural mechanisms underlying maladaptive eating behaviour.