TY - JOUR
T1 - Identification of a Brainstem Circuit Controlling Feeding
AU - Nectow, Alexander R.
AU - Schneeberger, Marc
AU - Zhang, Hongxing
AU - Field, Bianca C.
AU - Renier, Nicolas
AU - Azevedo, Estefania
AU - Patel, Bindiben
AU - Liang, Yupu
AU - Mitra, Siddhartha
AU - Tessier-Lavigne, Marc
AU - Han, Ming Hu
AU - Friedman, Jeffrey M.
N1 - Funding Information:
We thank Mats Ekstrand for help designing pAAV-IV-GFPL10, Brad Lowell, Linh Vong, and Dong Kong for contributing VGLUT3-IRES-Cre and Vgat-IRES-Cre mice, Chitra Kumar and Varun Bhave for help with chemogenetic studies, Karl Deisseroth for contributing pAAV-EF1a-DIO-ChR2-mCherry, used in the creation of pAAV-IV-GFPL10, Todd Anthony and David Anderson for contributing the virus AAV5-EF1a-‘Cre-out’-ChR2-EYFP, Masago Ishikawa and Paul Kenny for help with electrophysiology, Ilana Witten and Eric Nestler for helpful discussions, and The Rockefeller University Genomics and Bio-Imaging Resource Centers. This work is supported by funding from The JPB foundation (CEN 5402133; J.M.F.). A.R.N. acknowledges support from the David Rockefeller Fellowship, the Brain and Behavior Research Foundation NARSAD Young Investigator Award, the Princeton Neuroscience Institute's CV Starr Fellowship and Innovation Award, and The Rockefeller University's Shapiro-Silverberg Fund (CEN5301493). H.Z is supported by the National Natural Science Foundation of China (81200862). M.H.H. acknowledges support from the NIMH (R01MH092306), NIAA, and the Brain and Behavior Research Foundation NARSAD Independent Investigator Award (21464).
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/7/27
Y1 - 2017/7/27
N2 - Hunger, driven by negative energy balance, elicits the search for and consumption of food. While this response is in part mediated by neurons in the hypothalamus, the role of specific cell types in other brain regions is less well defined. Here, we show that neurons in the dorsal raphe nucleus, expressing vesicular transporters for GABA or glutamate (hereafter, DRNVgat and DRNVGLUT3 neurons), are reciprocally activated by changes in energy balance and that modulating their activity has opposite effects on feeding—DRNVgat neurons increase, whereas DRNVGLUT3 neurons suppress, food intake. Furthermore, modulation of these neurons in obese (ob/ob) mice suppresses food intake and body weight and normalizes locomotor activity. Finally, using molecular profiling, we identify druggable targets in these neurons and show that local infusion of agonists for specific receptors on these neurons has potent effects on feeding. These data establish the DRN as an important node controlling energy balance.
AB - Hunger, driven by negative energy balance, elicits the search for and consumption of food. While this response is in part mediated by neurons in the hypothalamus, the role of specific cell types in other brain regions is less well defined. Here, we show that neurons in the dorsal raphe nucleus, expressing vesicular transporters for GABA or glutamate (hereafter, DRNVgat and DRNVGLUT3 neurons), are reciprocally activated by changes in energy balance and that modulating their activity has opposite effects on feeding—DRNVgat neurons increase, whereas DRNVGLUT3 neurons suppress, food intake. Furthermore, modulation of these neurons in obese (ob/ob) mice suppresses food intake and body weight and normalizes locomotor activity. Finally, using molecular profiling, we identify druggable targets in these neurons and show that local infusion of agonists for specific receptors on these neurons has potent effects on feeding. These data establish the DRN as an important node controlling energy balance.
KW - body weight
KW - dorsal raphe nucleus
KW - energy homeostasis
KW - feeding
KW - leptin resistance
KW - locomotor activity
KW - obesity
UR - http://www.scopus.com/inward/record.url?scp=85026366756&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2017.06.045
DO - 10.1016/j.cell.2017.06.045
M3 - Article
C2 - 28753423
AN - SCOPUS:85026366756
SN - 0092-8674
VL - 170
SP - 429-442.e11
JO - Cell
JF - Cell
IS - 3
ER -