Universität zu Köln

Reinoss, Philip, Ciglieri, Elisa, Minere, Marielle, Bremser, Stephan, Klein, Andreas, Lohr, Heiko, Fuller, Patrick M., Büschges, Ansgar ORCID: 0000-0003-2123-1900, Kloppenburg, Peter, Fenselau, Henning and Hammerschmidt, Matthias (2020). Hypothalamic Pomc Neurons Innervate the Spinal Cord and Modulate the Excitability of Premotor Circuits. Current Biology, 30 (23). 4579 - 4593.e7. CAMBRIDGE: CELL PRESS. ISSN 1879-0445

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Abstract

Locomotion requires energy, yet animals need to increase locomotion in order to find and consume food in energy-deprived states. While such energy homeostatic coordination suggests brain origin, whether the central melanocortin 4 receptor (Mc4r) system directly modulates locomotion through motor circuits is unknown. Here, we report that hypothalamic Pomc neurons in zebrafish andmice have long-range projections into spinal cord regions harboring Mc4r-expressing V2a interneurons, crucial components of the premotor networks. Furthermore, in zebrafish, Mc4r activation decreases the excitability of spinal V2a neurons as well as swimming and foraging, while systemic or V2a neuron-specific blockage of Mc4r promotes locomotion. In contrast, in mice, electrophysiological recordings revealed that two-thirds of V2a neurons in lamina X are excited by the Mc4r agonist alpha-MSH, and acute inhibition of Mc4r signaling reduces locomotor activity. In addition, we found other Mc4r neurons in spinal lamina X that are inhibited by alpha-MSH, which is in line with previous studies in rodents where Mc4r agonists reduced locomotor activity. Collectively, our studies identify spinal V2a interneurons as evolutionary conserved second-order neurons of the central Mc4r system, providing a direct anatomical and functional link between energy homeostasis and locomotor control systems. The net effects of this modulatory system on locomotor activity can vary between different vertebrate species and, possibly, even within one species. We discuss the biological sense of this phenomenon in light of the ambiguity of locomotion on energy balance and the different living conditions of the different species.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Reinoss, Philip UNSPECIFIED UNSPECIFIED UNSPECIFIED Ciglieri, Elisa UNSPECIFIED UNSPECIFIED UNSPECIFIED Minere, Marielle UNSPECIFIED UNSPECIFIED UNSPECIFIED Bremser, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Lohr, Heiko UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuller, Patrick M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Büschges, Ansgar UNSPECIFIED orcid.org/0000-0003-2123-1900 UNSPECIFIED Kloppenburg, Peter UNSPECIFIED UNSPECIFIED UNSPECIFIED Fenselau, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Hammerschmidt, Matthias UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-308535
DOI:	10.1016/j.cub.2020.08.103
Journal or Publication Title:	Current Biology
Volume:	30
Number:	23
Page Range:	4579 - 4593.e7
Date:	2020
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	1879-0445
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Zoologisches Institut
Subjects:	Life sciences
Uncontrolled Keywords:	Keywords Language ENERGY HOMEOSTASIS; EXCITATORY INTERNEURONS; UNDERLYING LOCOMOTION; ANTAGONIST SHU9119; LARVAL ZEBRAFISH; V2A INTERNEURONS; MOTOR-NEURONS; IN-VIVO; NUCLEUS; OBESITY Multiple languages Biochemistry & Molecular Biology; Biology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/30853