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

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 and Bong-June Yoon ()
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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

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-023-44322-8

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