Faculty Profiles - FUKUSHIMA Akihiro

Presentations -

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視索前野EP3ニューロンの温度感受性

福島章紘，中村佳子，中村和弘

第51回自律神経生理研究会 2024.12.7

Thermosensitivity of preoptic EP3 neurons

Akihiro Fukushima, Yoshiko Nakamura, Kazuhiro Nakamura

2024.9.21

In vivo single-cell 3D optogenetics technology with light-field microscopy International conference

Tomoyoshi Inoue, Ryuki Imamura, Naoya Kataoka, Akihiro Fukushima, Shin Usuki, Takuma Sugi

21st IUPAB Congress 2024 (IUPAB2024) 2024.6

Oxytocinergic nervous system that facilitates sympathetic thermogenesis

Akihiro Fukushima, Kazuhiro Nakamura

第101回日本生理学会大会 2024.3.28

褐色脂肪熱産生を駆動するオキシトシン神経系

福島章紘, 中村和弘

温熱生理研究会 2023.9.21

Tonic GABAergic signaling from prostaglandin EP3 receptor-expressing preoptic neurons bidirectionally controls body temperature International conference

Kazuhiro Nakamura, Yoshiko Nakamura, Takaki Yahiro, Akihiro Fukushima, Naoya Kataoka, Hiroyuki Hioki

American Physiology Summit 2023.4 American Physiological Society

Event date： 2023.4

Language：English Presentation type：Oral presentation (general)

Venue：Long Beach Country：United States

The main controller neurons of the thermoregulatory center in the preoptic area (POA) have yet to be determined. In the present study using rats, we discovered that prostaglandin EP3 receptor-expressing POA neurons (POAEP3R neurons) are a pivotal bidirectional controller in the central thermoregulatory circuit mechanism. POAEP3R neurons were activated in response to elevated ambient temperature, but inhibited by prostaglandin E2, a pyrogenic mediator. In newly generated Ptger3-tTA transgenic rats, chemogenetic stimulation of POAEP3R neurons at room temperature reduced body temperature by eliciting skin vasodilation (enhancing heat dissipation), whereas inhibition of them elicited hyperthermia involving brown adipose tissue thermogenesis and tachycardia, mimicking fever. Furthermore, we revealed that POAEP3R neurons innervate sympathoexcitatory neurons in the dorsomedial hypothalamus (DMH) via tonic inhibitory signaling. Although many POAEP3R neuronal cell bodies expressed a glutamatergic mRNA marker, paradoxically, most of their axons in the DMH contained GABAergic synaptic proteins. Interestingly, GABAergic terminals of POAEP3R→DMH axons were increased by chronic heat exposure of rats, indicating a synaptic alteration to enhance heat tolerance. Consistent with the anatomical observation, slice patch-clamp recordings combined with optogenetic stimulation of POAEP3R→DMH axon terminals showed that these terminals predominantly form GABAergic synapses onto DMH neurons. These findings demonstrate that tonic GABAergic inhibitory signaling from POAEP3R neurons is a fundamental determinant of body temperature for thermal homeostasis and fever.

体温調節の多臓器反応を統合的に制御する中枢ニューロン

中村和弘、中村佳子、八尋貴樹、福島章紘

日本生理学会第100回記念大会 2023.3.16 日本生理学会

Event date： 2023.3

Presentation type：Oral presentation (general)

Venue：京都 Country：Japan

The central mechanism for integrated control of multi-organ responses is unknown. Using rats, here we show that prostaglandin EP3 receptor-expressing neurons in the thermoregulatory center, preoptic area (POA) (POAEP3R neurons) are an integrated controller of multi-organ responses for thermal homeostasis. POAEP3R neurons were activated in response to elevated ambient temperature, but inhibited by prostaglandin E2, a pyrogenic mediator. Chemogenetic stimulation of POAEP3R neurons at room temperature reduced body temperature by eliciting skin vasodilation, whereas inhibition of them elicited hyperthermia involving brown fat thermogenesis and tachycardia, mimicking fever. We found that POAEP3R neurons innervate sympathoexcitatory neurons in the dorsomedial hypothalamus (DMH) via tonic inhibitory signaling. Although many POAEP3R neuronal cell bodies expressed a glutamatergic mRNA marker, their axons in the DMH predominantly released GABA and their GABAergic terminals were increased by chronic heat exposure. These findings demonstrate that tonic GABAergic inhibitory signaling from POAEP3R neurons is a fundamental determinant of body temperature for thermal homeostasis and fever.

体温の中枢制御システムの基本原理

中村佳子、八尋貴樹、福島章紘、片岡直也、日置寛之、中村和弘

第17回環境生理学プレコングレス 2023.3.13

褐色脂肪熱産生を駆動するオキシトシン神経系

福島章紘

Biothermology Workshop 2022 & 温度生物学若手の会合同シンポジウム 2022.12.26

A central oxytocin neural pathway that regulates metabolism

Akihiro Fukushima, Kazuhiro Nakamura

The 3rd CIBoG Retreat 2022.2.19

Oxytocinergic pathway stimulating brown adipose tissue thermogenesis

Fukushima A, Nakamura K

the 126th Annual Meeting of The Japanese Association of Anatomists / the 98th Annual Meeting of The Physiological Society of Japan 2021.3.29

Event date： 2021.3

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

Venue：Web

Endothermic animals maintain their core body temperature by controlling skin vasomotion and brown adipose tissue (BAT) thermogenesis. These thermoregulatory organs are regulated by sympathetic inputs from the hypothalamo-medullary-spinal central pathway. Oxytocin (OXT), a hypothalamic neuropeptide, contributes to a variety of behaviors and stress responses. Impairment of the oxytocinergic (OXTergic) neural system leads to metabolic hypofunction. However, the neuronal pathway underpinning the link between OXT and metabolism has not been determined. To elucidate the mechanism, we performed neural tract tracing and in vivo BAT sympathetic recording in combination with optogenetic stimulation of a specific OXTergic neural pathway, and found that (i) OXT neurons in a dorsocaudal part of the paraventricular hypothalamic nucleus innervate sympathetic premotor neurons in the rostral medullary raphe region (rMR); (ii) the OXTergic input to the rMR stimulates BAT thermogenesis by potentiating glutamatergic transmission onto sympathetic premotor neurons. This OXTergic pathway may underlie etiologies of metabolic disorders, such as Prader-Willi syndrome, and be relevant to emotional responses.

How do emotions impact thermogenic and cardiovascular functions?

Nakamura K, Kataoka N, Fukushima A

The 98th Annual Meeting of The Physiological Society of Japan 2021.3.28

Event date： 2021.3

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

Venue：Web

Emotions strongly impact thermogenic and cardiovascular functions by affecting the central sympathetic regulatory system. We have discovered a central neural pathway that mediates psychological stress signaling by connecting the corticolimbic emotion circuit to the hypothalamomedullary autonomic regulatory system. This is a master psychosomatic pathway that drives a variety of sympathetic and behavioral stress responses, such as brown adipose tissue (BAT) thermogenesis, tachycardia, and pressor response. Recently, we have also identified a central circuit mechanism by which the oxytocin nervous system, which is stimulated by emotional cues, impacts metabolic and cardiac functions. In vivo optogenetic and physiological studies revealed that oxytocinergic inputs from the hypothalamus to medullary sympathetic premotor neurons stimulate BAT thermogenic and cardiac responses by potentiating glutamatergic sympathoexcitatory efferent transmission. Based on these findings, we will discuss central psychosomatic circuit mechanisms that underlie a variety of phenomena due to “mind?body” relationship in health and disease.

Oxytocinergic Neurons in the Hypothalamic Paraventricular Nucleus Stimulate Brown Adipose Tissue Thermogenesis through Rostral Medullary Raphe

Fukushima A, Nakamura K

2020.10

視床下部室傍核オキシトシン神経系による褐色脂肪熱産生の促進

福島章紘，中村和弘

第10回名古屋大学医学系研究科・生理学研究所合同シンポジウム 2020.9.19

視床下部室傍核オキシトシン神経系による褐色脂肪熱産生の促進

福島章紘，中村和弘

温熱生理研究会 2020.8.27 生理学研究所

Oxytocinergic Transmission from Paraventricular Hypothalamic Nucleus to Rostral Medullary Raphe Stimulates Brown Adipose Tissue Thermogenesis

Fukushima A, Nakamura K

The 97th Annual Meeting of the Physiological Society of Japan 2020.3

Oxytocinergic Transmission from the Paraventricular Hypothalamic Nucleus to Rostral Medullary Raphe Stimulates Brown Adipose Tissue Thermogenesis

Akihiro Fukushima, Kazuhiro Nakamura

2020.3.16

Central Neural Pathways for Thermoregulation and Beyond. Invited

Akihiro Fukushima

2019.11.21

Oxytocinergic Neurons in the Hypothalamic Paraventricular Nucleus Stimulate Brown Adipose Tissue Thermogenesis Through Rostral Medullary Raphe

Fukushima A, Nakamura K

第9回名古屋大学医学系研究科・生理学研究所合同シンポジウム 2019.9.28

Oxytocinergic Neurons in the Hypothalamic Paraventricular Nucleus Stimulate Brown Adipose Tissue Thermogenesis through Rostral Medullary Raphe International conference

Fukushima A, Nakamura K

Experimental Biology 2019 Meeting 2019.4

Event date： 2019.4

Language：English Presentation type：Poster presentation

Venue：Orlando, USA Country：United States

Hypothalamic neurons in the paraventricular nucleus (PVN) produce several neuropeptides, including oxytocin and vasopressin, and send their axons to various brain regions. These PVN neurons have been considered to serve neuroendocrine and autonomic functions, and many studies have demonstrated the involvement of oxytocin in social and emotional behaviors (e.g. maternal and sexual behaviors, and stress responses). Although these behaviors are accompanied with autonomic responses, it is unclear how oxytocin modulates the activities of the autonomic nervous system. To investigate the roles of PVN oxytocinergic neurons in the central regulation of autonomic function, in this study, we first performed neural tract tracing in rats from PVN oxytocinergic neurons to the rostral medullary raphe region (rMR), which contains sympathetic premotor neurons controlling brown adipose tissue (BAT) thermogenesis. In the rMR, oxytocin‐immunoreactive fibers, but not vasopressin‐immunoreactive fibers, were distributed, and oxytocin‐containing terminals were apposed to tryptophan hydroxylase‐expressing (i.e., serotonergic) neurons, potentially BAT sympathetic premotor neurons. Retrograde tracing from the rMR with cholera toxin b‐subunit (CTb) labeled a portion of oxytocinergic neurons in the caudal PVN, but not in the supraoptic nucleus, suggesting that the PVN is a major source of oxytocinergic fibers in the rMR. Then, we performed in vivo BAT sympathetic nerve recording combining optogenetic stimulation of the PVN‐derived oxytocinergic axon terminals in the rMR. Recombinant adeno‐associated viral vectors were injected into the PVN to express the engineered channel rhodopsin variant, ChIEF, under the oxytocin promoter. We confirmed that most of PVN neurons expressing ChIEF‐mCherry contained oxytocin and that their axon fibers were densely distributed in the rMR. Optogenetic stimulation of these fibers evoked BAT sympathetic nerve activities as well as increased expired CO2 and heart rate. Similar thermogenic and cardiac responses were elicited by nanoinjection of oxytocin into the rMR, and these responses were blocked by prior injection of the oxytocin receptor antagonist, L‐368,899 into the rMR. In addition, oxytocin injection into the rMR also potentiated NMDA‐evoked BAT sympathetic nerve activities. These findings indicate that PVN oxytocinergic neurons stimulate thermogenic sympathetic outflow to BAT through activation of rMR neurons. This oxytocinergic pathway may play an important role in emotion‐related autonomic responses.

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Presentations -