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Control of food approach and eating by a GABAergic projection from lateral hypothalamus to dorsal pons
Journal article   Open access   Peer reviewed

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 and Antonello Bonci
Proceedings of the National Academy of Sciences - PNAS, Vol.117(15), pp.8611-8615
04/14/2020
DOI: 10.1073/pnas.1909340117
PMCID: PMC7165479
PMID: 32229573
url
https://doi.org/10.1073/pnas.1909340117View
Published (Version of record) Open Access

Abstract

Stimulation of lateral hypothalamic (LH) neurons produces eating in sated animals and increases activity of dopamine neurons. The present study shows that the activation of dopamine neurons failed to induce eating. Rather, food approach and eating were observed via activation of LH fibers that project through the VTA, continuing caudally and terminating in a brainstem region medial to the locus coeruleus (LC). We found that activation of GABA neurons in this peri-LC region is both necessary and sufficient for LH stimulation-induced eating, whereas their role in normal homeostatic feeding appears negligible. These findings suggest that this circuit orchestrates just one of the multiple aspects of eating: a compulsive consumption of food in the absence of a physiological stimulus of hunger. 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.
 reward Biological Sciences VTA eating

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