Control of food approach and eating by a GABAergic projection from lateral hypothalamus to dorsal pons

Rosa Anna M. Marino, Ross A. McDevitt, Stephanie C. Gantz, Hui Shen, Marco Pignatelli, Wendy Xin, Roy A. Wise, Antonello Bonci

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)8611-8615
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number15
DOIs
StatePublished - Apr 14 2020

Keywords

  • Eating
  • LC
  • LH
  • Reward
  • VTA

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