Periodic Reporting for period 4 - FeedHypNet (Dynamic regulation of feeding behaviors in health and disease by top-down control of hypothalamic networks)
Reporting period: 2021-10-01 to 2023-03-31
Feeding behaviors represent a complex set of crucial for survival abilities required to meet upcoming nutritional demands. Eating disorders, such as anorexia nervosa, are widespread, difficult to treat and extremely dangerous, displaying the highest mortality rate of all psychiatric disorders and a very high relapse rate. Mechanisms of onset, progression and relapse of eating disorders are unknown. Feeding behaviors are regulated by hypothalamus, an evolutionary conservative brain region. While a role of neurochemically defined hypothalamic neurons in feeding has been recently studied, little is known about an adaptive regulation of hypothalamus by extrahypothalamic inputs. Further, it is not known how dynamic signaling in hypothalamus upon changing metabolic and environmental demands is organized to generate consistent adaptive behavior. The overarching goal of the action is to provide insight into neural mechanisms of healthy and pathological feeding behaviors. To do so we perform recordings of neuronal activity using electrophysiology and calcium imaging, as well as selectively manipulate neuronal activity using optogenetics.
We investigated a role of neural circuitries that translate cognitive-related information to the lateral hypothalamus during adaptive feeding behaviors. We found that inputs from the prefrontal cortex regulate activity of hypothalamic neurons and affect feeding-related behavior. Further, we investigate how metabolic demands changes upon reduction of food intake, or an exposure to a high-fat diet, affect the signaling from the top-down brain regions to the hypothalamus. We investigated these changes and the behavioral output at various time scales - from subsecond timing of neuronal network oscillations to changes of activity of the same, genetically defined neurons in the lateral hypothalamus across weeks. Further, we investigate how signaling in hypothalamus changes during development of anorexia nervosa symptoms and study consequences of optogenetically restored physiological signaling.
This innovative and interdisciplinary approach enables identification of neuronal circuits mediating feeding behavior in health and pathology, and thus gain insights into neuronal mechanisms of eating disorders.