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Medullary reticular GABAergic neurons that mediate hunger responses induced by hypothalamic neuropeptide Y
Author(s) -
Nakamura Yoshiko,
Yanagawa Yuchio,
Morrison Shaun F,
Nakamura Kazuhiro
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1040.4
Subject(s) - gabaergic , hypothalamus , thermogenesis , neuropeptide y receptor , medicine , endocrinology , neuroscience , rostral ventromedial medulla , biology , inhibitory postsynaptic potential , medulla oblongata , dorsal raphe nucleus , lateral hypothalamus , stimulation , neuropeptide , central nervous system , adipose tissue , serotonin , nociception , serotonergic , receptor , hyperalgesia
Hunger stimulates release of neuropeptide Y (NPY) in the paraventricular hypothalamus (PVH) from nerves derived from the arcuate nucleus. The NPY action in the PVH reduces energy expenditure through inhibition of brown adipose tissue (BAT) thermogenesis and stimulates food intake—hunger responses to survive starvation. However, the central circuit mechanism by which the NPY‐mediated hunger signaling from the hypothalamus coordinates the autonomic and somatic motor systems to reduce energy expenditure and to drive the consummatory responses is unknown. In this study, using rats and mice, we found that hypothalamic action of NPY activates GABAegic neurons in the intermediate and parvicellular reticular nuclei (IRt/PCRt) of the medulla oblongata that project to the rostral medullary raphe, which contains sympathetic premotor neurons controlling BAT thermogenesis. Selective stimulation of GABAergic neurons in the IRt/PCRt with a chemogenetic technique inhibited cooling‐induced BAT thermogenesis. Inactivation of IRt/PCRt neurons eliminated the inhibitory effect of NPY action in the PVH on cooling‐induced BAT thermogenesis. Intriguingly, the GABAergic IRt/PCRt neurons innervating the BAT sympathetic premotor region also innervated the masticatory motor region, and stimulation of the IRt/PCRt elicited mastication and increased feeding as well as inhibition of BAT thermogenesis. These results demonstrate a hunger response central circuit in which NPY‐triggered signaling from the hypothalamus activates GABAergic IRt/PCRt neurons, which then inhibit the thermogenic sympathetic premotor drive to BAT to reduce energy expenditure and stimulate a masticatory motor drive for feeding. Support or Funding Information Grants‐in‐Aid for Scientific Research from MEXT, Japan (16H05128, 15H05932 & 15K21744 to KN, 26290002 & 15H01415 to YY, 26860159 to YN); NIH grant (R01NS40987 to SFM); Takeda Science Foundation (KN & YY); Uehara Memorial Foundation (KN).