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標題: | 研究未定區在前扣帶皮質前端抑制下而緩解神經性疼痛的角色 Investigation of the role of zona incerta in mediating aACC photoinhibition-induced neuropathic pain relief |
作者: | Yi-Jui Peng 彭顗睿 |
指導教授: | 姚皓傑(Hau-Jie Yau) |
關鍵字: | 神經性疼痛,光遺傳學,前扣帶皮層吻部,未定區,依賴神經活性之標定法, neuropathic pain,optogenectic,anterior cingulate cortex(aACC),zona incerta (ZI),activity-dependent targeting (TRAP), |
出版年 : | 2021 |
學位: | 碩士 |
摘要: | 已知前扣帶皮層 (ACC) 在疼痛感知中很重要,而抑制前扣帶皮層在神經性疼痛的老鼠具有相當的止痛作用。但是,前扣帶皮層抑制而造成止痛的神經迴路機制仍舊不清楚。另一方面,近來研究顯示未定區(zona incerta)的活化可以減輕神經性慢性疼痛。實驗室先前的研究指出,前扣帶皮層吻部有神經投射至未定區。而且以光遺傳學方法抑制從前扣帶皮層吻部到未定區的神經輸入,可以緩解神經性損傷的老鼠之機械性痛覺過敏。在我的論文第一部分研究,我探討以光遺傳學方法抑制前扣帶皮層吻部是否會活化未定區來緩解機械性痛覺過敏。為了驗證這個可能性,我使用仰賴神經性活性的標定技術(TRAP)將抑制性光敏感蛋白表現在受前扣帶皮層吻部抑制下而被活化的未定區細胞。我發現抑制這群被標定的未定區細胞降低前扣帶皮層吻部抑制所誘發的止痛效果。同樣的,非專一性的未定區抑制也能降低前扣帶皮層吻部抑制所誘發的止痛效果。綜合上述,這些結果支持我的假設:前扣帶皮層吻部抑制會透過一個去抑制的機制來活化未定區來緩解神經性疼痛。 在我的論文第二部分研究,我利用逆行性標定技術,發現有一小群的前扣帶皮層吻部細胞,其軸突側枝會同時投射到未定區和中腦導水管周圍灰質 (PAG)。而抑制這一小群前扣帶皮層吻部細胞也能緩解機械性痛覺過敏。 Anterior cingulate cortex (ACC) is known to play a critical role in pain perception and ACC inhibition has a profound pain-relieving effect in several animal models of neuropathic pain. Nevertheless, the descending circuit mechanisms mediating ACC inhibition-induced pain relief remain unclear. On the other hand, zona incerta (ZI) has recently been shown to attenuate mechanical allodynia while activated. Previous studies in the lab have shown that there exists a direct projection from anterior part of ACC (aACC) to zona incerta (ZI) and photoinhibition of aACC-to-ZI input relieves mechanical hyperalgesia in mice with spared nerve injury (SNI). In the first part of my thesis study, I investigated whether aACC inhibition may recruit ZI to alleviate neuropathic pain. To test this possibility, I employed activity-dependent targeting approach (Targeted Recombination in Active Population, TRAP) to selectively express halorhodopsin in ZI neurons activated by aACC photoinhibition. I found that photoinhibition of these TRAPed ZI neurons attenuated aACC photoinhibition-induced pain relief. Similarly, non-selective ZI photoinhibition also abolished aACC photoinhibition-induced pain relief. Taken together, these results support the hypothesis that aACC inhibition may recruit ZI through a disinhibition mechanism to alleviate neuropathic pain. In the second part of my thesis study, by using retrograde tracing, I have selectively targeted a subpopulation of aACC neurons sending axonal collaterals to both ZI and periaqueductal grey (PAG) and found that photoinhibition of this specific subpopulation of aACC neurons alleviated mechanical hyperalgesia in SNI mice. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/20176 |
DOI: | 10.6342/NTU202100743 |
全文授權: | 未授權 |
顯示於系所單位: | 腦與心智科學研究所 |
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