TY - JOUR
T1 - Distinctive Regulation of Emotional Behaviors and Fear-Related Gene Expression Responses in Two Extended Amygdala Subnuclei With Similar Molecular Profiles
AU - Ueda, Shuhei
AU - Hosokawa, Masahito
AU - Arikawa, Koji
AU - Takahashi, Kiyofumi
AU - Fujiwara, Mao
AU - Kakita, Manami
AU - Fukada, Taro
AU - Koyama, Hiroaki
AU - Horigane, Shin Ichiro
AU - Itoi, Keiichi
AU - Kakeyama, Masaki
AU - Matsunaga, Hiroko
AU - Takeyama, Haruko
AU - Bito, Haruhiko
AU - Takemoto-Kimura, Sayaka
N1 - Funding Information:
This work was supported by the KAKENHI grants under the grant numbers, JP16H04670, JP20H03339 (ST-K), JP20K15929 (SU), JP17H06312 (HB), and JP16H06276 (AdAMS to HB and ST-K); the Japan Science and Technology Agency (JST) PRESTO under grant numbers JPMJPR15F6 (ST-K) and JPMJPR15FA (MH); the Platform Project for Supporting Drug Discovery and Life Science Research [Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)] from AMED, JP21am0101104 (to HT); the Mishima Kaiun Memorial Foundation (ST-K); the Asahi Glass Foundation (ST-K); the Takeda Science Foundation (ST-K); and the Toray Science Foundation (ST-K). The supercomputing resource was provided by the Human Genome Center (University of Tokyo).
Publisher Copyright:
© Copyright © 2021 Ueda, Hosokawa, Arikawa, Takahashi, Fujiwara, Kakita, Fukada, Koyama, Horigane, Itoi, Kakeyama, Matsunaga, Takeyama, Bito and Takemoto-Kimura.
PY - 2021/9/3
Y1 - 2021/9/3
N2 - The central nucleus of the amygdala (CeA) and the lateral division of the bed nucleus of the stria terminalis (BNST) are the two major nuclei of the central extended amygdala that plays essential roles in threat processing, responsible for emotional states such as fear and anxiety. While some studies suggested functional differences between these nuclei, others showed anatomical and neurochemical similarities. Despite their complex subnuclear organization, subnuclei-specific functional impact on behavior and their underlying molecular profiles remain obscure. We here constitutively inhibited neurotransmission of protein kinase C-δ-positive (PKCδ+) neurons—a major cell type of the lateral subdivision of the CeA (CeL) and the oval nucleus of the BNST (BNSTov)—and found striking subnuclei-specific effects on fear- and anxiety-related behaviors, respectively. To obtain molecular clues for this dissociation, we conducted RNA sequencing in subnuclei-targeted micropunch samples. The CeL and the BNSTov displayed similar gene expression profiles at the basal level; however, both displayed differential gene expression when animals were exposed to fear-related stimuli, with a more robust expression change in the CeL. These findings provide novel insights into the molecular makeup and differential engagement of distinct subnuclei of the extended amygdala, critical for regulation of threat processing.
AB - The central nucleus of the amygdala (CeA) and the lateral division of the bed nucleus of the stria terminalis (BNST) are the two major nuclei of the central extended amygdala that plays essential roles in threat processing, responsible for emotional states such as fear and anxiety. While some studies suggested functional differences between these nuclei, others showed anatomical and neurochemical similarities. Despite their complex subnuclear organization, subnuclei-specific functional impact on behavior and their underlying molecular profiles remain obscure. We here constitutively inhibited neurotransmission of protein kinase C-δ-positive (PKCδ+) neurons—a major cell type of the lateral subdivision of the CeA (CeL) and the oval nucleus of the BNST (BNSTov)—and found striking subnuclei-specific effects on fear- and anxiety-related behaviors, respectively. To obtain molecular clues for this dissociation, we conducted RNA sequencing in subnuclei-targeted micropunch samples. The CeL and the BNSTov displayed similar gene expression profiles at the basal level; however, both displayed differential gene expression when animals were exposed to fear-related stimuli, with a more robust expression change in the CeL. These findings provide novel insights into the molecular makeup and differential engagement of distinct subnuclei of the extended amygdala, critical for regulation of threat processing.
KW - anxiety
KW - bed nucleus of the stria terminalis
KW - central extended amygdala
KW - central nucleus of the amygdala
KW - fear
KW - gene expression
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U2 - 10.3389/fnmol.2021.741895
DO - 10.3389/fnmol.2021.741895
M3 - Article
AN - SCOPUS:85115195679
SN - 1662-5099
VL - 14
JO - Frontiers in Molecular Neuroscience
JF - Frontiers in Molecular Neuroscience
M1 - 741895
ER -