Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41598-017-05327-8

Web of Science

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.cmet.2016.12.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The anxiolytic diazepam selectively inhibits psychological stress-induced autonomic and behavioral responses without causing noticeable suppression of other central performances. This pharmacological property of diazepam led us to the idea that neurons that exhibit diazepam-sensitive, psychological stress-induced activation are potentially those recruited for stress responses. To obtain neuroanatomical clues for the central stress circuitries, we examined the effects of diazepam on psychological stress-induced neuronal activation in broad brain regions. Rats were exposed to a social defeat stress, which caused an abrupt increase in body temperature by up to 2 C. Pretreatment with diazepam (4 mg/kg, i.p.) attenuated the stress-induced hyperthermia, confirming an inhibitory physiological effect of diazepam on the autonomic stress response. Subsequently, the distribution of cells expressing Fos, a marker of neuronal activation, was examined in 113 forebrain and midbrain regions of these rats after the stress exposure and diazepam treatment. The stress following vehicle treatment markedly increased Fos-immunoreactive (IR) cells in most regions of the cerebral cortex, limbic system, thalamus, hypothalamus and midbrain, which included parts of the autonomic, neuroendocrine, emotional and arousal systems. The diazepam treatment significantly reduced the stress-induced Fos expression in many brain regions including the prefrontal, sensory and motor cortices, septum, medial amygdaloid nucleus, medial and lateral preoptic areas, parvicellular paraventricular hypothalamic nucleus, dorsomedial hypothalamus, perifornical nucleus, tuberomammillary nucleus, association, midline and intralaminar thalami, and median and dorsal raphe nuclei. In contrast, diazepam increased Fos-IR cells in the central amygdaloid nucleus, medial habenular nucleus, ventromedial hypothalamic nucleus and magnocellular lateral hypothalamus. These results provide important information for elucidating the neural circuitries that mediate the autonomic and behavioral responses to psychosocial stressors. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.neuroscience.2014.04.047

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1152/ajpheart.00262.2011

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.1460-9568.2011.07863.x

Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The central mechanism of fever induction is triggered by an action of prostaglandin E(2) (PGE(2)) on neurons in the preoptic area (POA) through the EP3 subtype of prostaglandin E receptor. EP3 receptor (EP3R)-expressing POA neurons project directly to the dorsomedial hypothalamus (DMH) and to the rostral raphe pallidus nucleus (rRPa), key sites for the control of thermoregulatory effectors. Based on physiological findings, we hypothesize that the febrile responses in brown adipose tissue (BAT) and those in cutaneous vasoconstrictors are controlled independently by separate neuronal pathways: PGE2 pyrogenic signaling is transmitted from EP3R-expressing POA neurons via a projection to the DMH to activate BAT thermogenesis and via another projection to the rRPa to increase cutaneous vasoconstriction. In this case, DMH-projecting and rRPa-projecting neurons would constitute segregated populations within the EP3R-expressing neuronal group in the POA. Here, we sought direct anatomical evidence to test this hypothesis with a double-tracing experiment in which two types of the retrograde tracer, cholera toxin b-subunit (CTb), conjugated with different fluorophores were injected into the DMH and the rRPa of rats and the resulting retrogradely labeled populations of EP3R-immunoreactive neurons in the POA were identified with confocal microscopy. We found substantial numbers of EP3R-immunoreactive neurons in both the DMH-projecting and the rRPa-projecting populations. However, very few EP3R-immunoreactive POA neurons were labeled with both the CTb from the DMH and that from the rRPa, although a substantial number of neurons that were not immunoreactive for EP3R were double-labeled with both CTbs. The paucity of the EP3R-expressing neurons that send collaterals to both the DMH and the rRPa suggests that pyrogenic signals are sent independently to these caudal brain regions from the POA and that such pyrogenic outputs from the POA reflect different control mechanisms for BAT thermogenesis and for cutaneous vasoconstriction by distinct sets of POA neurons. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.neuroscience.2009.03.041

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SOC NEUROSCIENCE  

Sympathetic premotor neurons directly control sympathetic preganglionic neurons (SPNs) in the intermediolateral cell column (IML) of the thoracic spinal cord, and many of these premotor neurons are localized in the medulla oblongata. The rostral ventrolateral medulla contains premotor neurons controlling the cardiovascular conditions, whereas rostral medullary raphe regions are a candidate source of sympathetic premotor neurons for thermoregulatory functions. Here, we show that these medullary raphe regions contain putative glutamatergic neurons and that these neurons directly control thermoregulatory SPNs. Neurons expressing vesicular glutamate transporter 3 (VGLUT3) were distributed in the rat medullary raphe regions, including the raphe magnus and rostral raphe pallidus nuclei, and mostly lacked serotonin immunoreactivity. These VGLUT3-positive neurons expressed Fos in response to cold exposure or to central administration of prostaglandin E-2, a pyrogenic mediator. Transneuronal retrograde labeling after inoculation of pseudorabies virus into the interscapular brown adipose tissue (BAT) or the tail indicated that those VGLUT3-expressing medullary raphe neurons innervated these thermoregulatory effector organs multisynaptically through SPNs of specific thoracic segments, and microinjection of glutamate into the IML of the BAT-controlling segments produced BAT thermogenesis. An anterograde tracing study further showed a direct projection of those VGLUT3-expressing medullary raphe neurons to the dendrites of SPNs. Furthermore, intra-IML application of glutamate receptor antagonists blocked BAT thermogenesis triggered by disinhibition of the medullary raphe regions. The present results suggest that VGLUT3-expressing neurons in the medullary raphe regions constitute excitatory neurons that could be categorized as a novel group of sympathetic premotor neurons for thermoregulatory functions, including fever.

DOI： 10.1523/JNEUROSCI.1219-04.2004

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Authorship：Lead author   Publishing type：Article, review, commentary, editorial, etc. (other)  

Authorship：Lead author,　Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Authorship：Lead author,　Corresponding author   Publishing type：Article, review, commentary, editorial, etc. (other)  

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：FEDERATION AMER SOC EXP BIOL  

Web of Science

Authorship：Lead author   Language：English   Publishing type：Research paper, summary (international conference)  

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：FEDERATION AMER SOC EXP BIOL  

Web of Science

Language：English   Publishing type：Research paper, summary (international conference)   Publisher：PHYSIOLOGICAL SOCIETY OF JAPAN  

The rostral ventromedial medulla (RVMM) sympathetically regulates thermogenesis in brown adipose tissue (BAT) and constriction of skin blood vessels. However, the sympathetic-related neurons in the RVMM remain to be identified. First, we found that vesicular glutamate transporter 3 (VGLUT3) -immunoreactive neurons in the rostral raphe pallidus nucleus and raphe magnus nucleus expressed Fos in response to both fever-inducing stimulus (central injection of prostaglandin E<SUB>2</SUB>) and cold-exposure (4°C, 4 hours) in rats. Most of the VGLUT3-expressing neurons were negative for serotonin immunoreactivity, and many of them were labeled trans-synaptically with pseudorabies virus inoculated into rat interscapular BAT or tail. Furthermore, we found that the VGLUT3-positive neurons directly project onto sympathetic preganglionic neurons in the intermediolateral cell column (IML) of the spinal cord; and that VGLUT3-positive axon terminals in the IML formed asymmetric synapses, suggesting the excitatory characteristics of the synapses. These results suggest that the rostral medullary raphe regions contain glutamatergic neurons that could be categorized as a novel group of sympathetic premotor neurons involved in fever induction and thermoregulation. <b>[Jpn J Physiol 54 Suppl:S196 (2004)]</b>

Event date： 2017.12

Presentation type：Symposium, workshop panel (nominated)  

Event date： 2017

Language：English   Presentation type：Symposium, workshop panel (nominated)  

Event date： 2016.3

Language：English   Presentation type：Symposium, workshop panel (nominated)  

Event date： 2012

Language：English   Presentation type：Symposium, workshop panel (nominated)  

Event date： 2009

Language：English   Presentation type：Symposium, workshop panel (nominated)  

Event date： 2009

Language：English   Presentation type：Symposium, workshop panel (nominated)  

Event date： 2005

Language：English   Presentation type：Symposium, workshop panel (nominated)