Control of food approach and eating by a GABAergic projection from lateral hypothalamus to dorsal pons
| Autor: | Wendy Xin, Roy A. Wise, Hui Shen, Antonello Bonci, Marco Pignatelli, Rosa Anna Maria Marino, Stephanie C. Gantz, Ross A. McDevitt |
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| Rok vydání: | 2020 |
| Předmět: |
Male
LH medicine.medical_specialty Lateral hypothalamus Dopamine LC Stimulation Substantia nigra Biology Mice Reward Internal medicine Neural Pathways medicine Animals GABAergic Neurons gamma-Aminobutyric Acid Multidisciplinary Behavior Animal Dopaminergic Neurons Dopaminergic digestive oral and skin physiology Ventral Tegmental Area Feeding Behavior Biological Sciences Receptors GABA-A eating Ventral tegmental area medicine.anatomical_structure Endocrinology nervous system Hypothalamic Area Lateral GABAergic Locus coeruleus Female VTA medicine.drug Neuroscience |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 |
| Popis: | Significance 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. |
| Databáze: | OpenAIRE |
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