Regulation of Energy Expenditure by Brainstem GABA Neurons

Marc Schneeberger, Luca Parolari, Tania Das Banerjee, Varun Bhave, Putianqi Wang, Bindiben Patel, Thomas Topilko, Zhuhao Wu, Chan Hee J. Choi, Xiaofei Yu, Kyle Pellegrino, Esteban A. Engel, Paul Cohen, Nicolas Renier, Jeffrey M. Friedman, Alexander R. Nectow

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8 Scopus citations

Abstract

Homeostatic control of core body temperature is essential for survival. Temperature is sensed by specific neurons, in turn eliciting both behavioral (i.e., locomotion) and physiologic (i.e., thermogenesis, vasodilatation) responses. Here, we report that a population of GABAergic (Vgat-expressing) neurons in the dorsolateral portion of the dorsal raphe nucleus (DRN), hereafter DRNVgat neurons, are activated by ambient heat and bidirectionally regulate energy expenditure through changes in both thermogenesis and locomotion. We find that DRNVgat neurons innervate brown fat via a descending projection to the raphe pallidus (RPa). These neurons also densely innervate ascending targets implicated in the central regulation of energy expenditure, including the hypothalamus and extended amygdala. Optogenetic stimulation of different projection targets reveals that DRNVgat neurons are capable of regulating thermogenesis through both a “direct” descending pathway through the RPa and multiple “indirect” ascending pathways. This work establishes a key regulatory role for DRNVgat neurons in controlling energy expenditure.

Original languageEnglish (US)
Pages (from-to)672-685.e12
JournalCell
Volume178
Issue number3
DOIs
StatePublished - Jul 25 2019

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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    Schneeberger, M., Parolari, L., Das Banerjee, T., Bhave, V., Wang, P., Patel, B., Topilko, T., Wu, Z., Choi, C. H. J., Yu, X., Pellegrino, K., Engel, E. A., Cohen, P., Renier, N., Friedman, J. M., & Nectow, A. R. (2019). Regulation of Energy Expenditure by Brainstem GABA Neurons. Cell, 178(3), 672-685.e12. https://doi.org/10.1016/j.cell.2019.05.048