Semaphorin 6D tunes amygdalar circuits for emotional, metabolic, and inflammatory outputs

Nakanishi, Yoshimitsu; Izumi, Mayuko; Matsushita, Hiroaki; Koyama, Yoshihisa; Diez, Diego; Takamatsu, Hyota; Koyama, Shohei; Nishide, Masayuki; Naito, Maiko; Mizuno, Yumiko; Yamaguchi, Yuta; Mae, Tomoki; Noda, Yu; Nakaya, Kamon; Nojima, Satoshi; Sugihara, Fuminori; Okuzaki, Daisuke; Ikawa, Masahito; Shimada, Shoichi; Kang, Sujin; Kumanogoh, Atsushi

doi:https://doi.org/10.1016/j.neuron.2024.06.017

Semaphorin 6D tunes amygdalar circuits for emotional, metabolic, and inflammatory outputs

Nakanishi, Yoshimitsu; Izumi, Mayuko; Matsushita, Hiroaki et al.

Neuron, 2024, 112(17), 2955-2972.e9

Number of Access:2,383（2025-07-27 12:37 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/98345

Link to primary information

File	Format	Terms of use	Size	Views	Date.Available	Description	information
Neuron_112_17_2955	pdf	None	9.67 MB	69	2024.10.29

Creative Commons : Attribution

Item Information

Output File Export EndNote Basic Export Mendeley

Title	Semaphorin 6D tunes amygdalar circuits for emotional, metabolic, and inflammatory outputs
Creator	NRID 1000070882645 1000070882645 researchmap permalink fdksdeij-adrf32cd fdksdeij-adrf32cd CreatorName Nakanishi, Yoshimitsu
	researchmap permalink m_izumi m_izumi CreatorName Izumi, Mayuko
	CreatorName Matsushita, Hiroaki
	NRID 1000040397667 1000040397667 researchmap permalink koyamayoshihisa koyamayoshihisa Scopus Author ID 49761644100 49761644100 CreatorName Koyama, Yoshihisa
	NRID 1000090597741 1000090597741 ORCID 0000-0002-2325-4893 0000-0002-2325-4893 researchmap permalink diego_diez diego_diez Scopus Author ID 34569502100 34569502100 CreatorName Diez, Diego
	NRID 1000030584411 1000030584411 researchmap permalink thyota thyota CreatorName Takamatsu, Hyota
	NRID 1000080767559 1000080767559 ORCID 0000-0002-6897-9417 0000-0002-6897-9417 researchmap permalink sk500 sk500 CreatorName Koyama, Shohei
	NRID 1000080812255 1000080812255 ORCID 0000-0001-6060-1228 0000-0001-6060-1228 researchmap permalink masayukinishide masayukinishide Scopus Author ID 37075377900 37075377900 CreatorName Nishide, Masayuki
	NRID 1000010974686 1000010974686 researchmap permalink maikonaito maikonaito CreatorName Naito, Maiko
	NRID 1000090991141 1000090991141 researchmap permalink mizunoyumiko mizunoyumiko CreatorName Mizuno, Yumiko
	researchmap permalink yuta-yamaguchi yuta-yamaguchi CreatorName Yamaguchi, Yuta
	CreatorName Mae, Tomoki
	CreatorName Noda, Yu
	CreatorName Nakaya, Kamon
	NRID 1000040528791 1000040528791 ORCID 0000-0002-5124-0026 0000-0002-5124-0026 researchmap permalink snojima snojima Scopus Author ID 16224082000 16224082000 CreatorName Nojima, Satoshi
	NRID 1000050381645 1000050381645 researchmap permalink sugiharaf sugiharaf CreatorName Sugihara, Fuminori
	NRID 1000000346131 1000000346131 ORCID 0000-0002-4552-783X 0000-0002-4552-783X researchmap permalink read0092307 read0092307 Scopus Author ID 6506703054 6506703054 CreatorName Okuzaki, Daisuke
	NRID 1000020304066 1000020304066 ORCID 0000-0001-9859-6217 0000-0001-9859-6217 researchmap permalink read0054910 read0054910 Scopus Author ID 16689054500 16689054500 CreatorName Ikawa, Masahito
	NRID 1000020216063 1000020216063 researchmap permalink 556shimada 556shimada Scopus Author ID 35452177800 35452177800 ORCID 0000-0001-5369-1069 0000-0001-5369-1069 CreatorName Shimada, Shoichi
	NRID 1000030644398 1000030644398 researchmap permalink sujinkang sujinkang Scopus Author ID 55731417400 55731417400 CreatorName Kang, Sujin
	NRID 1000010294125 1000010294125 researchmap permalink read0051725 read0051725 Scopus Author ID 6602726311 6602726311 ORCID 0000-0003-4749-7117 0000-0003-4749-7117 CreatorName Kumanogoh, Atsushi
Subject	amygdala
	anxiety
	brain
	myelopoiesis
	obesity
	semaphorin
	sympathetic nervous system
	synapse
	γ-aminobutyric acid
Description	Nakanishi Y., Izumi M., Matsushita H., et al. Semaphorin 6D tunes amygdalar circuits for emotional, metabolic, and inflammatory outputs. Neuron 112, 2955 (2024); https://doi.org/10.1016/j.neuron.2024.06.017.
Abstract	Regulated neural-metabolic-inflammatory responses are essential for maintaining physiological homeostasis. However, the molecular machinery that coordinates neural, metabolic, and inflammatory responses is largely unknown. Here, we show that semaphorin 6D (SEMA6D) coordinates anxiogenic, metabolic, and inflammatory outputs from the amygdala by maintaining synaptic homeostasis. Using genome-wide approaches, we identify SEMA6D as a pleiotropic gene for both psychiatric and metabolic traits in human. Sema6d deficiency increases anxiety in mice. When fed a high-fat diet, Sema6d−/− mice display attenuated obesity and enhanced myelopoiesis compared with control mice due to higher sympathetic activity via the β3-adrenergic receptor. Genetic manipulation and spatial and single-nucleus transcriptomics reveal that SEMA6D in amygdalar interneurons is responsible for regulating anxiogenic and autonomic responses. Mechanistically, SEMA6D is required for synaptic maturation and γ-aminobutyric acid transmission. These results demonstrate that SEMA6D is important for the normal functioning of the neural circuits in the amygdala, coupling emotional, metabolic, and inflammatory responses.
Publisher	Cell Press
Source Title	Neuron
Volume (Issue)	112(17)
Page	2955-2972.e9
Date of Issued	2024-09-01
Language	English
Handle URL	https://hdl.handle.net/11094/98345
PISSN	08966273
eISSN	10974199
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.neuron.2024.06.017
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCTERMS.bibliographicCitation	Neuron. 2024, 112(17), p. 2955-2972.e9
DC.title	Semaphorin 6D tunes amygdalar circuits for emotional, metabolic, and inflammatory outputs
DC.creator	Nakanishi, Yoshimitsu
	Izumi, Mayuko
	Matsushita, Hiroaki
	Koyama, Yoshihisa
	Diez, Diego
	Takamatsu, Hyota
	Koyama, Shohei
	Nishide, Masayuki
	Naito, Maiko
	Mizuno, Yumiko
	Yamaguchi, Yuta
	Mae, Tomoki
	Noda, Yu
	Nakaya, Kamon
	Nojima, Satoshi
	Sugihara, Fuminori
	Okuzaki, Daisuke
	Ikawa, Masahito
	Shimada, Shoichi
	Kang, Sujin
	Kumanogoh, Atsushi
DC.publisher	Cell Press
DC.language' scheme='DCTERMS.RFC1766	English
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-09-01
DC.identifier	https://doi.org/10.1016/j.neuron.2024.06.017
DC.subject	amygdala
	anxiety
	brain
	myelopoiesis
	obesity
	semaphorin
	sympathetic nervous system
	synapse
	γ-aminobutyric acid
DC.description	Nakanishi Y., Izumi M., Matsushita H., et al. Semaphorin 6D tunes amygdalar circuits for emotional, metabolic, and inflammatory outputs. Neuron 112, 2955 (2024); https://doi.org/10.1016/j.neuron.2024.06.017.
DCTERMS.abstract	Regulated neural-metabolic-inflammatory responses are essential for maintaining physiological homeostasis. However, the molecular machinery that coordinates neural, metabolic, and inflammatory responses is largely unknown. Here, we show that semaphorin 6D (SEMA6D) coordinates anxiogenic, metabolic, and inflammatory outputs from the amygdala by maintaining synaptic homeostasis. Using genome-wide approaches, we identify SEMA6D as a pleiotropic gene for both psychiatric and metabolic traits in human. Sema6d deficiency increases anxiety in mice. When fed a high-fat diet, Sema6d−/− mice display attenuated obesity and enhanced myelopoiesis compared with control mice due to higher sympathetic activity via the β3-adrenergic receptor. Genetic manipulation and spatial and single-nucleus transcriptomics reveal that SEMA6D in amygdalar interneurons is responsible for regulating anxiogenic and autonomic responses. Mechanistically, SEMA6D is required for synaptic maturation and γ-aminobutyric acid transmission. These results demonstrate that SEMA6D is important for the normal functioning of the neural circuits in the amygdala, coupling emotional, metabolic, and inflammatory responses.
DC.rights	This article is licensed under a Creative Commons Attribution 4.0 International License.
DC.format	98345
citation_title	Semaphorin 6D tunes amygdalar circuits for emotional, metabolic, and inflammatory outputs
citation_author	Nakanishi, Yoshimitsu
	Izumi, Mayuko
	Matsushita, Hiroaki
	Koyama, Yoshihisa
	Diez, Diego
	Takamatsu, Hyota
	Koyama, Shohei
	Nishide, Masayuki
	Naito, Maiko
	Mizuno, Yumiko
	Yamaguchi, Yuta
	Mae, Tomoki
	Noda, Yu
	Nakaya, Kamon
	Nojima, Satoshi
	Sugihara, Fuminori
	Okuzaki, Daisuke
	Ikawa, Masahito
	Shimada, Shoichi
	Kang, Sujin
	Kumanogoh, Atsushi
citation_publisher	Cell Press
citation_language	English
citation_date	2024-09-01
citation_journal_title	Neuron
citation_volume	112
citation_issue	17
citation_firstpage	2955
citation_lastpage	2972.e9
citation_doi	https://doi.org/10.1016/j.neuron.2024.06.017
citation_public_url	https://hdl.handle.net/11094/98345

Semaphorin 6D tunes amygdalar circuits for emotional, metabolic, and inflammatory outputs

Link to primary information

Item Information

Show details