1. Research Background:
Essential components of the control system that regulates body weight and energy balance are formed by small neuronal networks located in the hypothalamus. These control circuits adjust food intake and energy expenditure according to the organism's needs and the availability of fuel sources in the periphery of the body. A mismatch between energy intake and expenditure can cause metabolic disorders, including obesity and type 2 diabetes mellitus, whose prevalence is increasing in western societies. To better understand and counteract obesity and associated metabolic disorders, increasing efforts are being made to define the control mechanisms that regulate body weight and energy homeostasis.
2. Research questions addresses by the group:
Our research focuses on neuromodulation and how the plasticity of the neurocircuits in control of energy homeostasis is regulated on the cellular and molecular level on short time scales and during the lifespan. We are especially interested in the biophysical mechanisms that determine neuronal excitability and synaptic plasticity in this context. Our studies aim to understand how the modulation of intrinsic and synaptic properties of single neurons (or groups of neurons) regulates the function of complex neuronal systems and ultimately controls the (feeding) behavior of an organism.
3. Possible projects:
- Modulation of homeostasis regulating neurons by nutrients, endocrine factors, and sensory stimuli
- Integration of multiple extracellular signals in single neurons
- Intracellular Ca2+dynamics as a key regulator for neuronal excitability
- Intracellular Ca2+ handling as a target for metabolic modulation
4. Applied Methods and model organisms:
- Electro- and optophysiological recordings.
- Quantitative analysis of intracellular Ca2+ handling.
- Opto- and chemogenetics.
- Experiments are performed in vitro and in situ in mouse models.
5. Desirable skills and qualifications:
High interest in single-cell physiology and membrane biophysics.
- Hess S, Pouzat C, Paeger L, Pippow A, Kloppenburg P. Cell Calcium (2021) Analysis of neuronal Ca2+ handling properties by combining perforated patch clamp recordings and the added buffer approach. Cell Calcium. 97:102411. doi: 10.1016/j.ceca.2021.102411. Online ahead of print.
- Biglari N, Gaziano I, Schumacher J, Radermacher J, Paeger L, Klemm P, Chen W, Corneliussen S, Wunderlich CM, Sue M, Vollmar S, Klöckener T, Sotelo-Hitschfeld T, Abbasloo A, Edenhofer F, Reimann F, Gribble FM, Fenselau H, Kloppenburg P, Wunderlich FT, Brüning JC (2021) Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting. .Nat Neurosci. 24(7):913-929. doi: 10.1038/s41593-021-00854-0.
- Jais A, Paeger L, Sotelo-Hitschfeld T, Bremser S, Prinzensteiner M, Klemm P, Mykytiuk V, Widdershooven PJM, Vesting AJ, Grzelka K, Minère M, Cremer AL, Xu J, Korotkova T, Lowell BB, Zeilhofer HU, Backes H, Fenselau H, Wunderlich FT, Kloppenburg P, Brüning JC (2020) PNOCARC Neurons Promote Hyperphagia and Obesity upon High-Fat-Diet Feeding. Neuron 106(6):1009-1025.e10. doi: 10.1016/j.neuron.2020.03.022.
- Paeger L., Pippow A., Hess S., Paehler M., Klein A.C., Husch A., Pouzat C., Brüning J.C., Kloppenburg P. (2017b) Energy imbalance alterd Ca2+ handling and excitability of POMC neurons. eLlife 6. pii: e25641. doi: 10.7554/eLife.25641.
- Paeger, L., Karakasilioti, I., Altmüller, J., Frommolt, P., Brüning, J.C., Kloppenburg, P. (2017a). Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenaline. eLife 6. pii: e25770. doi: 10.7554/eLife.25770.
- Steculorum, S.M., Ruud, J., Karakasilioti, I., Backes, H., Engström Ruud, L., Timper, K., Hess, M.E., Tsaousidou, E., Mauer, J., Vogt, M.C., Paeger, L., Bremser, S., Klein, A.C., Morgan, D.A., Frommolt, P., Brinkkötter, P.T., Hammerschmidt, P., Benzing, T., Rahmouni, K., Wunderlich, F.T., Kloppenburg, P., Brüning J.C. (2016) AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue. Cell 165, 125–138.
- Hess M.E., Hess S., Meyer K.D., Verhagen L.A., Koch L., Brönneke H.S., Dietrich M.O., Jordan S.D., Saletore Y., Elemento O., Belgardt B.F., Franz T., Horvath T.L., Rüther U., Jaffrey S.R., Kloppenburg P., Brüning J.C. (2013) The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry. Nat Neurosci 16, 1042-8.