Studies on chemogenetic inhibition of the ACC excitatory neurons in a mouse model of inflammatory hyperalgesia induced by CFA
마우스 화학유전학을 통한 전대상피질 흥분성 뉴런들의 억제가 CFA로 유도된 염증성 통각과민에 미치는 효과

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자연과학대학 협동과정뇌과학전공
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chronic painhyperalgesiaDREADDsanterior cingulate cortexCFAhM4Divon Frey test
학위논문 (석사)-- 서울대학교 대학원 : 뇌과학협동과정, 2017. 2. 강봉균.
Many previous studies have shown that the anterior cingulate cortex (ACC) is involved in cognitive/emotional pain processing. Nonetheless, because of the heterogeneous composition and projections in the ACC, the underlying central mechanism that modulates chronic pain is still unclear. However, recent rodent model studies have demonstrated that the excitatory/inhibitory and temporal optogenetic modulation of excitatory neurons in the ACC can induce/alleviate hyperalgesia. Together with optogenetics, the designer receptors exclusively activated by designer drugs (DREADDs) system, which is chemogenetic tool, has been utilized for the long-term activation/inhibition of neuronal activities in many brain regions. Here, we first show that the chemogenetic inhibition of excitatory neurons in the ACC can reduce mechanical pain responses. To examine this, we injected inhibitory DREADD (hM4Di)-expressing adeno-associated virus (AAV) into the mouse ACC. After recovery from the surgery, we subcutaneously injected complete Freund's Adjuvant (CFA) into the right hind paw of mice to induce hyperalgesia and measured the changes in mechanical thresholds with electronic von Frey apparatus. Additionally, we calculated the ratio of c-Fos-positive hM4Di-mCherry- or mCherry-expressing neurons to total hM4Di-mCherry or mCherry-expressing neurons. By analyzing the changes in mechanical thresholds and relative neural activities represented by c-Fos, we demonstrated that reducing neural activity in excitatory neurons in the ACC could directly alleviate hyperalgesia induced by CFA. To our knowledge, this is the first study that has utilized chemogenetics to study chronic pain in the supraspinal region. In addition, these findings extend the available research tools for examining chronic pain. Moreover, this study successfully reproduced the results of studies on optogenetics.
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College of Natural Sciences (자연과학대학)Program in Brain Science (협동과정-뇌과학전공)Theses (Master's Degree_협동과정-뇌과학전공)
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