TY - JOUR
T1 - Control of food approach and eating by a GABAergic projection from lateral hypothalamus to dorsal pons
AU - Marino, Rosa Anna M.
AU - McDevitt, Ross A.
AU - Gantz, Stephanie C.
AU - Shen, Hui
AU - Pignatelli, Marco
AU - Xin, Wendy
AU - Wise, Roy A.
AU - Bonci, Antonello
N1 - Funding Information:
ACKNOWLEDGMENTS. We thank the National Institute on Drug Abuse (NIDA) breeding staff for breeding the transgenic animals, Hugo Tejeda and Leonardo Bontempi at NIDA Intramural Research Program (IRP), and Dennis R. Sparta and Sonia Aroni at the University of Maryland for their critical reading of the manuscript. This research was supported by the NIDA Intramural Research Program.
Publisher Copyright:
© 2020 National Academy of Sciences. All rights reserved.
PY - 2020/4/14
Y1 - 2020/4/14
N2 - Electrical or optogenetic stimulation of lateral hypothalamic (LH) GABA neurons induces rapid vigorous eating in sated animals. The dopamine system has been implicated in the regulation of feeding. Previous work has suggested that a subset of LH GABA neurons projects to the ventral tegmental area (VTA) and targets GABA neurons, inhibiting them and thereby disinhibiting dopaminergic activity and release. Furthermore, stimulation-induced eating is attenuated by dopamine lesions or receptor antagonists. Here we explored the involvement of dopamine in LH stimulation-induced eating. LH stimulation caused sated mice to pick up pellets of standard chow with latencies that varied based on stimulation intensity; once food was picked up, animals ate for the remainder of the 60-s stimulation period. However, lesion of VTA GABA neurons failed to disrupt this effect. Moreover, direct stimulation of VTA or substantia nigra dopamine cell bodies failed to induce food approach or eating. Looking further, we found that some LH GABA fibers pass through the VTA to more caudal sites, where they synapse onto neurons near the locus coeruleus (LC). Similar eating was induced by stimulation of LH GABA terminals or GABA cell bodies in this peri-LC region. Lesion of peri-LC GABA neurons blocked LH stimulation-induced eating, establishing them as a critical downstream circuit element for LH neurons. Surprisingly, lesions did not alter body weight, suggesting that this system is not involved in the hunger or satiety mechanisms that govern normal feeding. Thus, we present a characterization of brain circuitry that may promote overeating and contribute to obesity.
AB - Electrical or optogenetic stimulation of lateral hypothalamic (LH) GABA neurons induces rapid vigorous eating in sated animals. The dopamine system has been implicated in the regulation of feeding. Previous work has suggested that a subset of LH GABA neurons projects to the ventral tegmental area (VTA) and targets GABA neurons, inhibiting them and thereby disinhibiting dopaminergic activity and release. Furthermore, stimulation-induced eating is attenuated by dopamine lesions or receptor antagonists. Here we explored the involvement of dopamine in LH stimulation-induced eating. LH stimulation caused sated mice to pick up pellets of standard chow with latencies that varied based on stimulation intensity; once food was picked up, animals ate for the remainder of the 60-s stimulation period. However, lesion of VTA GABA neurons failed to disrupt this effect. Moreover, direct stimulation of VTA or substantia nigra dopamine cell bodies failed to induce food approach or eating. Looking further, we found that some LH GABA fibers pass through the VTA to more caudal sites, where they synapse onto neurons near the locus coeruleus (LC). Similar eating was induced by stimulation of LH GABA terminals or GABA cell bodies in this peri-LC region. Lesion of peri-LC GABA neurons blocked LH stimulation-induced eating, establishing them as a critical downstream circuit element for LH neurons. Surprisingly, lesions did not alter body weight, suggesting that this system is not involved in the hunger or satiety mechanisms that govern normal feeding. Thus, we present a characterization of brain circuitry that may promote overeating and contribute to obesity.
KW - Eating
KW - LC
KW - LH
KW - Reward
KW - VTA
UR - http://www.scopus.com/inward/record.url?scp=85083153901&partnerID=8YFLogxK
U2 - 10.1073/pnas.1909340117
DO - 10.1073/pnas.1909340117
M3 - Article
C2 - 32229573
AN - SCOPUS:85083153901
SN - 0027-8424
VL - 117
SP - 8611
EP - 8615
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 15
ER -