Center for Molecular Medicine Cologne

Tatiana Korotkova - C 10

Regulation of feeding in health and pathology by glucagon-like peptide-1 receptor-expressing cells in the lateral hypothalamus and the lateral septum

Introduction

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.

Our Aims

  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.

Project-Releated Publications

  1. Ponomarenko, A., Korotkova, T. (2018) Hunger is a gatekeeper of pain in the brain. News and views for Alhadeff et, Cell 2018. Nature, 556(7702), 445-446.
  2. Carus-Cadavieco, M., Gorbati, M., Ye, L., Bender, F., van der Veldt, S., Kosse, C., Börgers, C., Lee, S.Y., Ramakrishnan, C., Hu, Y., Denisova, N., Ramm, F., Volitaki, E., Burdakov, D., Deisseroth, K., Ponomarenko, A and Korotkova, T. (2017) Gamma oscillations organize top-down signalling to hypothalamus and enable food seeking. Nature, 542(7640), 232-236.
  3. Herrera, C.G., Carus-Cadavieco, M., Jego, S., Ponomarenko, A., Korotkova, T., Adamantidis, A. (2016)  Hypothalamic feed-forward inhibition of thalamocortical network controls arousal and consciousness. Nature Neuroscience, 19(2), 290-298.
  4. Bender, F., Gorbati, M., Carus-Cadavieco, M., Denisova, N., Gao, X., Holman, C., Korotkova, T.,Ponomarenko, A. (2015) Theta oscillations regulate speed of locomotion via hippocampus to lateral septum pathway. Nature Communications, 6, 8521.
Prof. Dr. Tatiana Korotkova CMMC Cologne
Prof. Dr. Tatiana Korotkova

Institute of Vegetative Physiology

Principal Investigator - C 10

Executive Board Member

+49 221 47 26253

Institute of Vegetative Physiology

Robert-Koch-Str. 39

50931 Cologne

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Curriculum Vitae (CV)

Publications on PubMed

Publications - Tatiana Korotkova

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