Henning Fenselau

Max Planck Institute for Metabolism Research, Policlinic for Endocrinology, Diabetes, and Preventive Medicine

Synapses and Metabolism

Synapses are the main conduit of information flow in the brain. The Fenselau lab investigates how transmission across these essential connections enables communication within neural circuits that control systemic metabolism. Our lab focuses on advancing our current understanding of synaptic transmission and synaptic plasticity in neural circuits that regulate food intake, energy expenditure and glucose homeostasis.

Research Focus

An organism’s ability to tightly coordinate systemic metabolism is critical for health and survival. Such coordination is achieved by multiple distinct neural cell populations that sense energy-related signals and relay this information to downstream brain sites to orchestrate diverse metabolic processes such as feeding behavior, energy expenditure and glucose homeostasis. To achieve this, it is essential that communication within these circuits is efficient and highly precise as well as appropriately adapted to energy and nutrient availability. The Fenselau lab investigates synapse physiology and synaptic plasticity – such as long-term potentiation – of discrete neural circuits that regulate metabolic processes.

Axons are like long and narrow roads connecting a main factory to outposts located far away. Avoiding traffic accidents and maintaining the efficiency of the outposts is essential during our lifetime. Understanding how this is achieved is at the core of our research.

Our Goals

The overarching goal of our research is to detail how synaptic communication within defined neural circuits relates the control of systemic metabolism. Furthermore, we aim to define how synaptic dysfunction in these circuits contributes to pathological conditions such as obesity or diabetes.To advance our current understanding of synapse physiology and synaptic plasticity in defined neural circuits, we combine various state-of-the-art neuroscience techniques with mouse genetic approaches. This powerful combination provides a direct means to causally relate synaptic communication in defined neural circuits with physiological processes at the cellular, tissue and organismal levels.

We are currently addressing the following three key fundamental research questions:

  • Deciphering the synaptic organization of neural gut-to-brain communication
  • Defining the functional significance of synaptic plasticity in feeding circuits
  • Unravelling the regulatory role of neuropeptides in metabolic pathways

To this end, we employ a wide range of diverse, but complementary methodologies, including brain slice electrophysiology, recombinase-expressing mice, AAV viral approaches, optogenetics, chemogenetics, and in vivo imaging techniques. The powerful combination of these approaches allows us to study synaptic communication in defined neural circuits that have a clear metabolic function. Further, these approaches enable us to study how synaptic transmission and synaptic plasticity within neural circuits could become dysregulated and how this relates to pathological conditions such as obesity or diabetes.


Key Publications

  1. Mirabella PN, Fenselau H. (2023) Advanced neurobiological tools to interrogate metabolism. Nat Rev Endocrinol. Nov;19(11):639-654. doi: 10.1038/s41574-023-00885-6. Epub 2023 Sep 6.
  2. Grzelka K, Wilhelms H, Dodt S, Dreisow ML, Madara JC, Walker SJ, Wu C, Wang D, Lowell BB, Fenselau H. (2023) A synaptic amplifier of hunger for regaining body weight in the hypothalamus. Cell Metab. 2023 May 2;35(5):770-785.e5.
  3. Borgmann B, Ciglieri E, Biglari N, Brandt C, Cremer AL, Backes H, Tittgemeyer M, Wunderlich FT, Brüning JC, Fenselau H (2021) Gut-brain communication by distinct sensory neurons differently controls feeding and glucose metabolism. Cell Metab. 2021 Jul 6;33(7):1466-1482.e7.
  4. Reinoß P, Ciglieri E, Minére M, Bremser S, Klein A, Löhr H, Fuller PM, Büschges A, Kloppenburg P, Fenselau H#, Hammerschmidt M# (2020) Hypothalamic Pomc Neurons Innervate the Spinal Cord and Modulate the Excitability of Premotor Circuits. Curr Biol. 2020 Dec 7;30(23):4579-4593.e7. (#joint corresponding authors)
  5. Fenselau H, Campbell JN, Verstegen AM, Madara JC, Xu J, Shah BP, Resch JM, Yang Z, Mandelblat-Cerf Y, Livneh Y and Lowell BB (2017) A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by α-MSH. Nat Neurosci. 2017 Jan;20(1):42-51.