Research Group Leader - MPI for Metabolism Research
Dr. Henning Fenselau
Max-Planck-Institut für Stoffwechselforschung
Gleueler Str. 50
The Fenselau laboratory focuses on advancing our current understanding of the brain circuits that regulate food intake and glucose metabolism. Our team studies synaptic physiology and synaptic plasticity – such as long-term potentiation – at defined synapses with a wide range of diverse, but complementary methodologies including electrophysiology and optogenetics. The ultimate goal of our research is to link synaptic transmission and synaptic plasticity in defined neuronal circuits with specific behavioral and metabolic responses.
Our research: Tightly coordinating energy and glucose homeostasis is critical for metabolic health and survival. This coordination is achieved by multiple distinct neuronal cell populations that sense nutrient and hormonal signals and relay this information to downstream brain sites to orchestrate diverse physiological processes such as food intake, energy expenditure and insulin sensitivity.
The Fenselau laboratory is currently pursuing two lines of research. On the one hand, we are studying the impact of caloric deprivation on synaptic function in defined hypothalamic circuits. We believe that hunger can be understood as a sequence of synaptic adaptions starting in the hypothalamus and expanding to other parts of the brain. In addition, we study obesity-induced synaptic plasticity in genetic models of obesity. This line of research aims at correlating changes in synaptic function to overeating and body weight gain.
Our successes: We are implementing a powerful combination of modern neuroscience approaches that allow us to study synaptic transmission in defined neuronal circuits that have a clear metabolic function. Notably, our current investigations are based on Dr. Fenselau’s previous discoveries demonstrating the importance of synaptic transmission and synaptic plasticity in hypothalamic circuits that control motivated behavior and metabolism.
Our goals: The overarching goal of our research is to understand in detail how synaptic transmission and synaptic plasticity within defined neural circuits controls our behavior towards food and how synaptic dysfunction in these circuits relates to pathological conditions such as obesity or diabetes.
Our methods/techniques: The Fenselau laboratory employs a wide range of methodologies, including brain slice electrophysiology, recombinase-expressing mice, AAV viral approaches, optogenetics, chemogenetics, and in vivo imaging techniques.
Figure 1: α-MSH postsynaptically increases excitatory input onto PVH-MC4R neurons. A, Experimental schematic of optogenetic brain slice experiment. Glutamatergic currents recorded from melanocortin-4 receptor (MC4R)-expressing satiety neurons in the paraventricular hypothalamus (PVH-MC4R neurons) upon blue light illumination. B, Representative traces of α-MSH effects on light-evoked AMPAR and NMDAR currents recorded from PVH-MC4R neurons.
Images taken from: Fenselau et al. (2017). A rapidly acting glutamatergic ARC→PVH satiety circuit postsynaptically regulated by a-MSH. Nat Neurosci. 2017 Jan;20(1):42-51.
Figure 2: A polysynaptic circuit by which the suprachiasmatic nucleus clock regulates behavioral aggression. A, Schematic drawing of the SCN→SPZ→VMH neural circuit. B, Top: Schematic shows connection that was tested. Bottom: Representative traces of light-evoked GABAergic currents before and after bath application of the GABA-A receptor antagonist bicuculline. SCN-VIP neurons were transduced with Channelrhodopsin-2 and VMH-projecting SPZ neurons were retrogradely labeled.
Images taken from: Todd and Fenselau et al. (2018). A hypothalamic circuit for the circadian control of aggression. Nat Neurosci. 2018 May;21(5):717-724.