Peter Kloppenburg

Institute for Zoology

Modulation of Neurocircuits

The central nervous system constantly integrates information about the internal milieu and the environment to optimize the organism's physiological state. Understanding the homeostasis-regulating neurocircuits and how they change during aging and disease fosters the identification of therapeutic strategies against metabolic disorders and their comorbidities, including neurological disorders.

Research Focus

Homeostasis of vital physiological parameters, including energy, is tightly controlled by specialized, highly adaptive neural circuits in the central nervous system. These neurocircuits acquire and integrate information about the internal milieu and the external environment. Based on this integrated information, they adjust their regulatory output to ensure optimal physiological homeostasis. Aging, extreme diets, and diseases can impair these homeostasis-regulating neuronal systems. These impairments drive the development of metabolic disorders such as obesity, type 2 diabetes, and associated comorbidities, including neurodegenerative diseases. By defining the physiological properties of these networks and their age and diet-related changes, our group aims to understand the molecular and cellular mechanisms that mediate the development of metabolic disorders.

A comprehensive understanding of the mechanisms that promote or prevent deregulation of these neuronal circuits helps to develop new therapeutic interventions against metabolic and neurological diseases.

Our Goals

As an overarching research topic, we focus on understanding the complex mechanisms regulating energy homeostasis and body weight. To this end, we are investigating how central neural circuits control food intake and energy expenditure, particularly under conditions that promote hyperphagia, obesity, and type 2 diabetes.

Our objectives include defining the biophysical and cellular mechanisms responsible for alterations in these neuronal circuits over the life span and how they are impacted by diet and other environmental factors, e.g., temperature.

  • At the systems level, this involves analyzing how information from multimodal sensory pathways is integrated into the energy homeostasis regulation system.
  • At the cellular and subcellular level, the objective is to explore the interplay of neuromodulators within neuronal circuits and their convergence on single neurons and to elucidate the interactions of different intracellular signaling pathways within single neurons.

Our research employs and combines optogenetics, chemogenetics, and various electrophysiological and optophysiological recording techniques to provide comprehensive mechanistic insights that can facilitate the development of therapeutic interventions for metabolic and neurological disorders.

Key Publications

  1. Hess, S., Pouzat, C., Paeger, L., Pippow, A., and Kloppenburg, P. (2021). Analysis of neuronal Ca2+ handling properties by combining perforated patch clamp recordings and the added buffer approach. Cell Calcium 97, 102411. 10.1016/j.ceca.2021.102411.
  2. Jais, A., Paeger, L., Sotelo-Hitschfeld, T., Bremser, S., Prinzensteiner, M., Klemm, P., Mykytiuk, V., Widdershooven, P.J.M., Vesting, A.J., Grzelka, K., Minère, M., Cremer, A.L., Xu, J., Korotkova, T., Lowell. B.B., Zeilhofer, H.U., Backes, H., Fenselau, H., Wunderlich, F.T., Kloppenburg, P., and Brüning, J.C. (2020). PNOCARC Neurons Promote Hyperphagia and Obesity upon High-Fat-Diet Feeding. Neuron 106, 1009-1025.e10. 10.1016/j.neuron.2020.03.022.
  3. Paeger, L., Pippow, A., Hess, S., Paehler, M., Klein, A.C., Husch, A., Pouzat, C., Brüning, J.C., and Kloppenburg, P. (2017). Energy imbalance alters Ca2+ handling and excitability of POMC neurons. Elife 6, e25641. 10.7554/eLife.25641.
  4. Steculorum, S.M., Paeger, L., Bremser, S., Evers, N., Hinze, Y., Idzko, M., Kloppenburg, P., and Brüning, J.C. (2015). Hypothalamic UDP Increases in Obesity and Promotes Feeding via P2Y6-Dependent Activation of AgRP Neurons. Cell. 162, 1404–1417. 10.1016/j.cell.2015.08.032.
  5. Kloppenburg, P., Zipfel, W.R., Webb, W.W., and Harris-Warrick, R.M. (2000). Highly localized Ca2+ accumulation revealed by multiphoton microscopy in an identified motoneuron and its modulation by dopamine. J Neurosci. 20, 2523–2533. 10.1523/JNEUROSCI.20-07-02523.2000.