Eating disorders and obesity represent a major health problem. Discoveries of neuronal pathways that decrease food intake acting on reward- and motivation-regulating neuronal circuits are crucial for anti-obesity treatment developments, since they will potentially limit overeating.

Further, inhibition of these circuits can increase the positive value of food, crucial for treatment of anorexia nervosa.

Unraveling of GLP-1R pathway functions may thus guide development of innovative therapies.

Eating disorders ranging from binge eating to anorexia nervosa represent a major health problem. Our previous work revealed that food consumption and feeding-related behaviors are regulated by the lateral hypothalamus and the lateral septum - brain regions that are also involved in reward processing (Carus-Cadavieco et al., Nature 2017). A subset of neurons in both regions expresses receptors to glucagone-like-peptide 1 (GLP-1R) - a peptide which inhibits food intake. The aim of the current proposal is to define the neuronal mechanism of GLP-1R action and causally investigate functions of GLP-1R-expressing neurons in health as well as during progression of obesity and anorexia nervosa.

We will combine state-of-the-art techniques including calcium imaging in behaving mice, optogenetics, chemogenetics and behavioral assays to causally link real-time operation of GLP-1 neuronal circuits in hypothalamic and motivation-related pathways with food intake and feeding-related behaviors. We will characterize spontaneous population dynamics of the GLP-1R-expressing cells in the lateral hypothalamus and the lateral septum, and define how these cells encode specific feeding-related behaviors at multiple time scales in health and pathology.

Further, we will unravel a causal role of GLP-1R cells in feeding-related behaviors, and investigate effects of GLP-1R receptors activation on neuronal activity of other feeding-related, neurochemically defined cell groups in the lateral hypothalamus and the lateral septum.

1. Characterize spontaneous population dynamics of the GLP-1R-expressing cells in the lateral hypothalamus and the lateral septum.
2. Define how these cells encode specific feeding-related behaviors at multiple scales in health and pathology.
3. Unravel a causal role of GLP-1R-expressing cells in feeding-related behaviors.
4. Investigate effects of GLP-1 receptor activation on neuronal activity of other feeding-related, neurochemically defined cell groups in the lateral hypothalamus.