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

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  • 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
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