IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-023-44322-8.html
   My bibliography  Save this article

Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice

Author

Listed:
  • In Bum Lee

    (Korea University)

  • Eugene Lee

    (Korea University)

  • Na-Eun Han

    (Korea University)

  • Marko Slavuj

    (Korea University)

  • Jeong Wook Hwang

    (Korea University)

  • Ahrim Lee

    (Korea University)

  • Taeyoung Sun

    (Korea University)

  • Yehwan Jeong

    (Korea University)

  • Ja-Hyun Baik

    (Korea University)

  • Jae-Yong Park

    (Korea University)

  • Se-Young Choi

    (Seoul National University School of Dentistry)

  • Jeehyun Kwag

    (Seoul National University)

  • Bong-June Yoon

    (Korea University)

Abstract

Compulsive behaviors are observed in a range of psychiatric disorders, however the neural substrates underlying the behaviors are not clearly defined. Here we show that the basolateral amygdala-dorsomedial striatum (BLA-DMS) circuit activation leads to the manifestation of compulsive-like behaviors. We revealed that the BLA neurons projecting to the DMS, mainly onto dopamine D1 receptor-expressing neurons, largely overlap with the neuronal population that responds to aversive predator stress, a widely used anxiogenic stressor. Specific optogenetic activation of the BLA-DMS circuit induced a strong anxiety response followed by compulsive grooming. Furthermore, we developed a mouse model for compulsivity displaying a wide spectrum of compulsive-like behaviors by chronically activating the BLA-DMS circuit. In these mice, persistent molecular changes at the BLA-DMS synapses observed were causally related to the compulsive-like phenotypes. Together, our study demonstrates the involvement of the BLA-DMS circuit in the emergence of enduring compulsive-like behaviors via its persistent synaptic changes.

Suggested Citation

  • In Bum Lee & Eugene Lee & Na-Eun Han & Marko Slavuj & Jeong Wook Hwang & Ahrim Lee & Taeyoung Sun & Yehwan Jeong & Ja-Hyun Baik & Jae-Yong Park & Se-Young Choi & Jeehyun Kwag & Bong-June Yoon, 2024. "Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44322-8
    DOI: 10.1038/s41467-023-44322-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-44322-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-44322-8?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Garret D. Stuber & Dennis R. Sparta & Alice M. Stamatakis & Wieke A. van Leeuwen & Juanita E. Hardjoprajitno & Saemi Cho & Kay M. Tye & Kimberly A. Kempadoo & Feng Zhang & Karl Deisseroth & Antonello , 2011. "Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking," Nature, Nature, vol. 475(7356), pages 377-380, July.
    2. Mark A. Ungless & Jennifer L. Whistler & Robert C. Malenka & Antonello Bonci, 2001. "Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons," Nature, Nature, vol. 411(6837), pages 583-587, May.
    3. Vincent Pascoli & Agnès Hiver & Ruud Zessen & Michaël Loureiro & Ridouane Achargui & Masaya Harada & Jérôme Flakowski & Christian Lüscher, 2018. "Stochastic synaptic plasticity underlying compulsion in a model of addiction," Nature, Nature, vol. 564(7736), pages 366-371, December.
    4. Patricia H. Janak & Kay M. Tye, 2015. "From circuits to behaviour in the amygdala," Nature, Nature, vol. 517(7534), pages 284-292, January.
    5. Jeffrey M. Welch & Jing Lu & Ramona M. Rodriguiz & Nicholas C. Trotta & Joao Peca & Jin-Dong Ding & Catia Feliciano & Meng Chen & J. Paige Adams & Jianhong Luo & Serena M. Dudek & Richard J. Weinberg , 2007. "Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice," Nature, Nature, vol. 448(7156), pages 894-900, August.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ren-Wen Han & Zi-Yi Zhang & Chen Jiao & Ze-Yu Hu & Bing-Xing Pan, 2024. "Synergism between two BLA-to-BNST pathways for appropriate expression of anxiety-like behaviors in male mice," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Mariusz Mucha & Anna E. Skrzypiec & Jaison B. Kolenchery & Valentina Brambilla & Satyam Patel & Alberto Labrador-Ramos & Lucja Kudla & Kathryn Murrall & Nathan Skene & Violetta Dymicka-Piekarska & Aga, 2023. "miR-483-5p offsets functional and behavioural effects of stress in male mice through synapse-targeted repression of Pgap2 in the basolateral amygdala," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Gayane Aghakhanyan & Paolo Bonanni & Giovanna Randazzo & Sara Nappi & Federica Tessarotto & Lara De Martin & Francesca Frijia & Daniele De Marchi & Francesco De Masi & Beate Kuppers & Francesco Lombar, 2016. "From Cortical and Subcortical Grey Matter Abnormalities to Neurobehavioral Phenotype of Angelman Syndrome: A Voxel-Based Morphometry Study," PLOS ONE, Public Library of Science, vol. 11(9), pages 1-17, September.
    4. Lahti, Tom & Halko, Marja-Liisa & Karagozoglu, Necmi & Wincent, Joakim, 2019. "Why and how do founding entrepreneurs bond with their ventures? Neural correlates of entrepreneurial and parental bonding," Journal of Business Venturing, Elsevier, vol. 34(2), pages 368-388.
    5. Allen P. F. Chen & Lu Chen & Kaiyo W. Shi & Eileen Cheng & Shaoyu Ge & Qiaojie Xiong, 2023. "Nigrostriatal dopamine modulates the striatal-amygdala pathway in auditory fear conditioning," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Kazuhisa Shibata & Takeo Watanabe & Mitsuo Kawato & Yuka Sasaki, 2016. "Differential Activation Patterns in the Same Brain Region Led to Opposite Emotional States," PLOS Biology, Public Library of Science, vol. 14(9), pages 1-27, September.
    7. Oliver Barnstedt & Petra Mocellin & Stefan Remy, 2024. "A hippocampus-accumbens code guides goal-directed appetitive behavior," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    8. Gwynne L. Davis & Adelaide R. Minerva & Argentina Lario & Linda D. Simmler & Carolyn I. Rodriguez & Lisa A. Gunaydin, 2021. "Ketamine increases activity of a fronto-striatal projection that regulates compulsive behavior in SAPAP3 knockout mice," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    9. Owen Y. Chao & Salil Saurav Pathak & Hao Zhang & George J. Augustine & Jason M. Christie & Chikako Kikuchi & Hiroki Taniguchi & Yi-Mei Yang, 2023. "Social memory deficit caused by dysregulation of the cerebellar vermis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    10. Kuikui Zhou & Hua Xu & Shanshan Lu & Shaolei Jiang & Guoqiang Hou & Xiaofei Deng & Miao He & Yingjie Zhu, 2022. "Reward and aversion processing by input-defined parallel nucleus accumbens circuits in mice," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    11. Lukas M. von Ziegler & Amalia Floriou-Servou & Rebecca Waag & Rebecca R. Gupta & Oliver Sturman & Katharina Gapp & Christina A. Maat & Tobias Kockmann & Han-Yu Lin & Sian N. Duss & Mattia Privitera & , 2022. "Multiomic profiling of the acute stress response in the mouse hippocampus," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    12. Sean C. Piantadosi & Elizabeth E. Manning & Brittany L. Chamberlain & James Hyde & Zoe LaPalombara & Nicholas M. Bannon & Jamie L. Pierson & Vijay M. K Namboodiri & Susanne E. Ahmari, 2024. "Hyperactivity of indirect pathway-projecting spiny projection neurons promotes compulsive behavior," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    13. Huiling Yu & Liping Chen & Huiyang Lei & Guilin Pi & Rui Xiong & Tao Jiang & Dongqin Wu & Fei Sun & Yang Gao & Yuanhao Li & Wenju Peng & Bingyu Huang & Guoda Song & Xin Wang & Jingru Lv & Zetao Jin & , 2022. "Infralimbic medial prefrontal cortex signalling to calbindin 1 positive neurons in posterior basolateral amygdala suppresses anxiety- and depression-like behaviours," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    14. Feng Zhou & Weihua Zhao & Ziyu Qi & Yayuan Geng & Shuxia Yao & Keith M. Kendrick & Tor D. Wager & Benjamin Becker, 2021. "A distributed fMRI-based signature for the subjective experience of fear," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    15. Kelsey M. Vollmer & Lisa M. Green & Roger I. Grant & Kion T. Winston & Elizabeth M. Doncheck & Christopher W. Bowen & Jacqueline E. Paniccia & Rachel E. Clarke & Annika Tiller & Preston N. Siegler & B, 2022. "An opioid-gated thalamoaccumbal circuit for the suppression of reward seeking in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    16. Dheeraj S. Roy & Young-Gyun Park & Minyoung E. Kim & Ying Zhang & Sachie K. Ogawa & Nicholas DiNapoli & Xinyi Gu & Jae H. Cho & Heejin Choi & Lee Kamentsky & Jared Martin & Olivia Mosto & Tomomi Aida , 2022. "Brain-wide mapping reveals that engrams for a single memory are distributed across multiple brain regions," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    17. Himanshu Gangal & Xueyi Xie & Zhenbo Huang & Yifeng Cheng & Xuehua Wang & Jiayi Lu & Xiaowen Zhuang & Amanda Essoh & Yufei Huang & Ruifeng Chen & Laura N. Smith & Rachel J. Smith & Jun Wang, 2023. "Drug reinforcement impairs cognitive flexibility by inhibiting striatal cholinergic neurons," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    18. Matthew T. Birnie & Annabel K. Short & Gregory B. Carvalho & Lara Taniguchi & Benjamin G. Gunn & Aidan L. Pham & Christy A. Itoga & Xiangmin Xu & Lulu Y. Chen & Stephen V. Mahler & Yuncai Chen & Talli, 2023. "Stress-induced plasticity of a CRH/GABA projection disrupts reward behaviors in mice," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    19. Lizhu Li & Lihui Lu & Yuqi Ren & Guo Tang & Yu Zhao & Xue Cai & Zhao Shi & He Ding & Changbo Liu & Dali Cheng & Yang Xie & Huachun Wang & Xin Fu & Lan Yin & Minmin Luo & Xing Sheng, 2022. "Colocalized, bidirectional optogenetic modulations in freely behaving mice with a wireless dual-color optoelectronic probe," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    20. Carole Morel & Sarah E. Montgomery & Long Li & Romain Durand-de Cuttoli & Emily M. Teichman & Barbara Juarez & Nikos Tzavaras & Stacy M. Ku & Meghan E. Flanigan & Min Cai & Jessica J. Walsh & Scott J., 2022. "Midbrain projection to the basolateral amygdala encodes anxiety-like but not depression-like behaviors," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-023-44322-8. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.