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Direct pathway from ventral medial prefrontal cortex to dorsomedial hypothalamus drives psychological stress‐induced hyperthermia
Author(s) -
Kataoka Naoya,
Nakamura Kazuhiro
Publication year - 2016
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.30.1_supplement.994.2
Subject(s) - bicuculline , neuroscience , prefrontal cortex , hypothalamus , rostral ventromedial medulla , endocrinology , optogenetics , muscimol , medicine , thermogenesis , chemistry , psychology , biology , gabaa receptor , receptor , hyperalgesia , nociception , adipose tissue , cognition
Psychological stress‐induced hyperthermia is a basic autonomic stress response observed in many mammals including humans. We have reported that stress induces thermogenesis in brown adipose tissue (BAT), hyperthermia and tachycardia by activating a direct neural pathway from the dorsomedial hypothalamus (DMH) to the rostral medullary raphe (rMR) (Kataoka et al. Cell Metabolism , 2014). However, the mechanism by which stress signals activate the DMH neurons driving the sympathetic stress responses remains unknown. In this study, we sought for the upper neurons that provide the DMH with such psychological stress inputs. Retrograde tracing with the retrograde neural tracer, cholera toxin b‐subunit (CTb) revealed numerous projections from the medial prefrontal cortex (mPFC) to the DMH. Stimulation of mPFC neurons with a nanoinjection of bicuculline, a GABA A receptor antagonist, in anesthetized rats increased BAT sympathetic nerve activity, BAT temperature and heart rate. These bicuculline‐evoked sympathetic responses were eliminated by bilateral inhibition of DMH neurons with muscimol nanoinjections. Importantly, rats exposed to social defeat stress, a sociopsychological stress model, exhibited expression of Fos, a marker for neuronal activation, in DMH‐projecting neurons in the ventral part of the mPFC (vmPFC), and inhibition of vmPFC neurons with muscimol nanoinjections strongly reduced BAT thermogenesis and hyperthermia evoked by social defeat stress in free‐moving rats. In contrast, inhibition of neurons in the infralimbic cortex, a dorsal part of the mPFC, exhibited a weaker inhibitory effect on these stress responses. Furthermore, selective stimulation of vmPFC–DMH monosynaptic transmission using an in vivo optogenetic technique elicited BAT thermogenesis and heart rate. These results indicate that the vmPFC–DMH monosynaptic pathway provides the DMH with stress signals to activate the DMH–rMR sympathoexcitatory pathway driving BAT thermogenesis for the development of stress‐induced hyperthermia. Support or Funding Information NEXT Program (LS070), KAKENHI (21890114, 22689007, 24790233, 26118508, 26713009), Nakajima Foundation, Takeda Science Foundation, and Kowa Life Science Foundation