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A ventral medial prefrontal cortex–dorsomedial hypothalamus monosynaptic pathway that drives sympathetic stress responses
Author(s) -
Kataoka Naoya,
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.717.3
Subject(s) - neuroscience , optogenetics , glutamatergic , social defeat , hypothalamus , prefrontal cortex , rostral ventromedial medulla , psychology , glutamate receptor , medicine , receptor , hyperalgesia , nociception , cognition
Psychological stress causes a variety of sympathetic responses in mammals, which help the body react quickly and effectively to the stressor. 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). However, the mechanism by which stress signals activate the DMH neurons driving the sympathetic stress responses remains unknown. Here we demonstrate that the ventral medial prefrontal cortex (vmPFC) is a major source of the stress signals to the DMH by performing in vivo physiological, optogenetic and neuroanatomical experiments in rats. Indicating the importance of glutamatergic inputs to the DMH in sympathetic stress responses, blockade of glutamate receptors in the DMH with bilateral nanoinjections of AP5/CNQX diminished BAT thermogenesis and hyperthermia evoked by social defeat stress, a sociopsychological stress model. Retrograde neural tracing from the DMH revealed numerous projections from the mPFC to the DMH, and anterograde tracing visualized putative synaptic connections of vmPFC‐derived glutamatergic axons to DMH neurons projecting to the rMR. Rats exposed to social defeat stress exhibited increased expression of Fos, a marker for neuronal activation, in DMH‐projecting neurons in the vmPFC, and inactivation of vmPFC neurons with bilateral muscimol nanoinjections diminished BAT thermogenic, hyperthermic, tachycardic and pressor responses evoked by social defeat stress. In contrast, inhibition of neurons in the dorsal part of the mPFC (dmPFC) exhibited a weaker inhibitory effect on these stress responses. Selective stimulation of vmPFC–DMH monosynaptic transmission using an in vivo optogenetic technique elicited BAT thermogenesis and tachycardia, which were both blocked by bilateral AP5/CNQX injections into the DMH. However, selective stimulation of dmPFC–DMH transmission did not increase BAT thermogenesis or tachycardia. These results indicate that the vmPFC–DMH glutamatergic monosynaptic pathway provides the DMH with excitatory stress signals to activate the DMH– rMR sympathoexcitatory pathway driving sympathetic stress responses. Support or Funding Information Funding: Grants‐in‐Aids for Scientific Research from MEXT, Japan (16K19006 to NK, 16H05128 & 15H05932 to KN); Takeda Science Foundation (KN); Uehara Memorial Foundation (KN); Brain Science Foundation (KN).