Acute and Prolonged Functional and Structural Plasticity in Central Energy Homeostasis Regulating Neuronal Circuits
Food intake is tightly controlled by defined neuronal circuits in the brain to adjust food intake and energy expenditure according to the availability of fuel sources in the periphery of the body. Aging, extreme diets, and diseases can deregulate these neuronal systems. To understand what makes organisms susceptible to metabolic disorders, it is essential to define age and diet-associated changes in this network. Accordingly, our goal is to define the mechanisms that regulate body weight and energy homeostasis, and assess how these control mechanisms change under pathophysiological conditions.
Potential projects focus on neuromodulation and the question of how 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. In this context, we are especially interested in the biophysical mechanisms that determine neuronal excitability and synaptic plasticity. The aim of our studies is to understand how the modulation of intrinsic and synaptic properties of single neurons (or groups of neurons) regulate the function of complex neuronal systems and ultimately control the (feeding) behavior of an organism.
Methodology & Research Model
State of the art electro- and optophysiological recordings in mouse models.
Requirements for Application
Keen interest in single cell physiology and membrane biophysics.
Paeger L, Pippow A, Hess S, Paehler M, Klein AC, Husch A, Pouzat C, Brüning JC, Kloppenburg P Energy imbalance alters Ca2+handling and excitability of POMC neurons. Elife. 2017 Aug 1;6. pii: e25641. doi: 10.7554/eLife.25641.
Paeger L, Karakasilioti I, Altmüller J, Frommolt P, Brüning J, Kloppenburg P. Antagonistic modulation of NPY/AgRP and POMC neurons in the arcuate nucleus by noradrenalin. Elife. 2017 Jun 20;6. pii: e25770. doi: 10.7554/eLife.25770.
Steculorum SM, Ruud J, Karakasilioti I, Backes H, Engström Ruud L, Timper K, Hess M, Tsaousidiou E, Mauer J, Vogt MC, Paeger L, Bremser S, Klein A, Morgan DA, Frommolt P, Brinkkötter PT, Benzing T, Rahmouni K, Wunderlich FT, Kloppenburg P, Brüning JC (2016) AgRP-Neurons Control Systemic Insulin Sensitivity via Myostatin-Expression in BAT. Cell. 165, 125-38.
SteculorumSM, Paeger L, Bremser S, Evers Hinze Y, Idzko M, Kloppenburg P, Brüning JC. (2015) Hypothalamic UDP-Production is Increased in Obesity and Promotes Feeding via P2Y6-Dependent Activation of Orexigenic AgRP-Neurons.Cell,162, 1404-17.
Hess ME, Hess S, Meyer KD, Verhagen LA, Koch L, Brönneke HS, Dietrich MO, Jordan SD, Saletore Y, Elemento O, Belgardt BF, Franz T, Horvath TL, Rüther U, Jaffrey SR, Kloppenburg P, Brüning JC. (2013) The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry. Nat. Neurosci.16, 1042-8.