基本情報
- 所属
- 自治医科大学 医学部生理学講座 神経脳生理学部門 助教
- 学位
- 博士(理学)
- 連絡先
- inutsukajichi.ac.jp
- J-GLOBAL ID
- 201201092406674474
- researchmap会員ID
- B000221305
社会行動と情動の関わりに関して、視床下部に存在するオレキシンやオキシトシンといった神経ペプチド産生ニューロンの機能を研究しています。手法としてはウイルスベクターとトランスジェニックマウス・ラットの組み合わせを使うことが多いです。神経回路特異的な活動操作・活動記録をすることで、複雑な生理機能を解きほぐしていきたいと考えています。最近は新たな分子ツールを作って既存の課題に別ルートから挑戦することも好みです。
研究分野
1経歴
4-
2015年6月 - 現在
-
2015年4月 - 2015年5月
-
2012年4月 - 2015年3月
-
2010年4月 - 2012年3月
学歴
3-
2007年4月 - 2010年3月
-
2005年4月 - 2007年3月
-
2001年4月 - 2005年3月
委員歴
3-
2024年 - 現在
-
2022年2月 - 現在
論文
30-
Frontiers in Behavioral Neuroscience 18 2024年9月23日Parental behavior comprises a set of crucial actions essential for offspring survival. In this study, a double transgenic mouse model engineered to specifically express channelrhodopsin-2 (ChR2) in paraventricular hypothalamic nucleus (PVN)–oxytocin neurons and ablate lateral hypothalamic area (LHA)–melanin-concentrating hormone (MCH) neurons was used to determine the relationship between PVN–oxytocin neurons and LHA–MCH neurons associated with parental behavior. Optogenetic stimulation of ChR2-expressing PVN–oxytocin neurons induces typical parental behavior with intact LHA–MCH neurons. However, after the partial ablation of LHA–MCH neurons, even optogenetic stimulation of PVN–oxytocin neurons failed to induce parental behavior in virgin male mice, resulting in neglect rather than parental behavior. Furthermore, approximately half of the subjects exhibited burying behavior toward pups, suggesting that pups became aversive stimuli, and male mice actively performed burying behavior to avoid these aversive stimuli. This study emphasizes the novel aspect of oxytocin neurons that could result in neglect in the absence of LHA–MCH neurons regulation.
-
Molecular brain 17(1) 41-41 2024年6月28日 査読有り筆頭著者責任著者The cerebellum plays an important role in cognitive and social functioning. Childhood damage in the cerebellum increases the risk of autism spectrum disorder. Cerebellar inflammation induces social avoidance in mice. Oxytocin regulates social relationship and expression pattern of the oxytocin receptor in the brain is related to social behaviors. However, the expression patterns of the oxytocin receptor in the cerebellum remain controversial. Here, we report that the expression patterns of the oxytocin receptor in the cerebellum are highly variable among knock-in transgenic lines. We used Oxtr-Cre knock-in mice combined with a fluorescent reporter line and found that oxytocin receptor expression in Bergmann glia was more variable than that in Purkinje cells. We found that physical damage with inflammation induced the selective upregulation of the oxytocin receptor in Bergmann glia. Our findings indicate high variability in oxytocin receptor expression in the cerebellum and suggest that the oxytocin receptor can affect neural processing in pathological conditions, such as inflammation.
-
Acta histochemica et cytochemica 57(2) 85-88 2024年4月25日 査読有りRecent advances in viral vector technology, specifically using adeno-associated virus (AAV) vectors, have significantly expanded possibilities in neuronal tracing. We have utilized the Cre/loxP system in combination with AAV techniques in rats to explore the subcellular localization of palmitoylation signal-tagged GFP (palGFP) in oxytocin-producing neurosecretory neurons. A distinctive branching pattern of single axons was observed at the level of the terminals in the posterior pituitary. Despite challenges in detecting palGFP signals by fluorescent microscopy, immunoelectron microscopy demonstrated predominant localization on the plasma membrane, with a minor presence on the neurosecretory vesicle membrane. These findings suggest that membrane-anchored palGFP may undergo exocytosis, translocating from the plasma membrane to the neurosecretory vesicle membrane. In this study, we observed characteristic axon terminal structures in the posterior pituitary of oxytocin neurons. This study indicates the importance of understanding the plasma membrane-specific sorting system in neuronal membrane migration and encourages future studies on the underlying mechanisms.
-
Frontiers in behavioral neuroscience 17 1289520-1289520 2023年 査読有りThe security of animal habitats, such as burrows and nests, is vital for their survival and essential activities, including eating, mating, and raising offspring. Animals instinctively exhibit defensive behaviors to protect themselves from imminent and potential threats. In 1963, researchers reported wild rats sealing the entrances to their burrows from the inside using materials such as mud, sand, and vegetation. This behavior, known as "entrance sealing (ES)," involves repetitive movements of their nose/mouth and forepaws and is likely a proactive measure against potential intruders, which enhances burrow security. These observations provide important insights into the animals' ability to anticipate potential threats that have not yet occurred and take proactive actions. However, this behavior lacks comprehensive investigation, and the neural mechanisms underpinning it remain unclear. Hypothalamic perifornical neurons expressing urocortin-3 respond to novel objects/potential threats and modulate defensive responses to the objects in mice, including risk assessment and burying. In this study, we further revealed that chemogenetic activation of these neurons elicited ES-like behavior in the home-cage. Furthermore, behavioral changes caused by activating these neurons, including manifestations of ES-like behavior, marble-burying, and risk assessment/burying of a novel object, were effectively suppressed by selective serotonin-reuptake inhibitors. The c-Fos analysis indicated that ES-like behavior was potentially mediated through GABAergic neurons in the lateral septum. These findings underscore the involvement of hypothalamic neurons in the anticipation of potential threats and proactive defense against them. The links of this security system with the manifestation of repetitive/stereotypic behaviors and the serotonergic system provide valuable insights into the mechanisms underlying the symptoms of obsessive-compulsive disorder.
-
Communications Biology 5(1) 2022年9月16日 査読有り筆頭著者責任著者Abstract Transgenic animals expressing fluorescent proteins are widely used to label specific cells and proteins. By using a split Cre recombinase fused with mCherry-binding nanobodies or designed ankyrin repeat proteins, we created Cre recombinase dependent on red fluorescent protein (RFP) (Cre-DOR). Functional binding units for monomeric RFPs are different from those for polymeric RFPs. We confirmed selective target RFP-dependent gene expression in the mouse cerebral cortex using stereotaxic injection of adeno-associated virus vectors. In estrogen receptor-beta (Esr2)-mRFP1 mice and gastrin-releasing peptide receptor (Grpr)-mRFP1 rats, we confirmed that Cre-DOR can be used for selective tracing of the neural projection from RFP-expressing specific neurons. Cellular localization of RFPs affects recombination efficiency of Cre-DOR, and light and chemical-induced nuclear translocation of an RFP-fused protein can modulate Cre-DOR efficiency. Our results provide a method for manipulating gene expression in specific cells expressing RFPs and expand the repertory of nanobody-based genetic tools.
MISC
46-
糖尿病・内分泌プラクティスWeb はじめに ストレスは食欲や睡眠といった生理現象に大きな影響を与え、行動面での変化にもつながる。こうした生理応答や行動変容においては、ストレスによって脳内で分泌される神経ペプチドが重要な役割を果たしている。 2023年7月
書籍等出版物
6共同研究・競争的資金等の研究課題
24-
日本学術振興会 科学研究費助成事業 基盤研究(B) 2022年4月 - 2026年3月
-
日本学術振興会 科学研究費助成事業 基盤研究(C) 2022年4月 - 2025年3月
-
公益財団法人 喫煙科学研究財団 2020年4月 - 2023年3月
-
公益財団法人 栃木県産業振興センター 令和4年度 世界一を目指す研究開発助成事業 2022年7月 - 2023年2月
-
日本学術振興会 科学研究費助成事業 基盤研究(B) 2019年4月 - 2022年3月