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題名 時間關聯的操作式制約行為之神經機制：以c-Fos免疫組織化學染色法為例
Neural mechanisms of the operant conditioned behavior based on temporal contingency: by c-Fos immunohistochemistry作者 鍾居翰
Chung, Chu Hang貢獻者 廖瑞銘
Liao, Ruey Ming
鍾居翰
Chung, Chu Hang關鍵詞 區辨性增強低頻反應作業
行為抑制
計時
習得歷程
differential reinforcement of low-rate responding task
behavioral inhibition
timing
acquisition
c-Fos日期 2008 上傳時間 19-Sep-2009 11:54:33 (UTC+8) 摘要 區辨性增強低頻反應作業 (differential reinforcement of low-rate responding task, DRL task) 為一與時間相關聯之操作式制約行為作業，該作業常用於計時行為、行為抑制功能、或抗焦慮與抗憂鬱症等藥物之行為藥理研究的探討。雖然DRL作業是一種實驗室常用的動物行為模式，但是對於上述行為或藥理機制的探討往往缺乏一致性的解釋，其中可能的原因為DRL作業的行為同時包含了計時與行為抑制的成份。針對上述問題，本研究將以DRL行為作業為研究主題，探討作業習得歷程之神經機制。首先根據DRL作業之行為內涵，將作業的習得分為行為抑制與計時先後表現的兩個階段；並依據過去的研究文獻整理出的八個與行為抑制和計時表現相關之大腦區塊，以c-Fos免疫組織化學染色法探討行為抑制和計時的神經機制。實驗結果發現受試於行為抑制的表現階段，其眶眼皮質、內側前額葉皮質、與海馬CA1區域的c-Fos表現量較高；而在計時行為的表現階段，除了和行為抑制有關的三個大腦區塊外，尚有前扣帶迴、紋狀體、與齒狀迴呈現c-Fos表現量增加的現象。綜合以上結果，DRL-10秒作業於學習初期所進行的行為抑制可能和前額葉皮質與海馬體的神經互動有關；而學習較末階段的計時表現，則可能需要前額葉皮質、紋狀體、與海馬等三處較多的次級區域的組織加入，形成神經網路的方式支援之。
Differential reinforcement of low-rate responding (DRL) task was an operant conditioned behavior based on temporal contingency. This task has been widely used to investigate the behavioral components of timing and behavioral inhibition, which is frequently used for pharmacological screening of anxiolytic and antidepressant drugs. Despite of being widely used as an animal behavioral model in the laboratory, but the performance of the DRL task was varied and inconsistent when the drug test conducted. One way to encounter this problematic issue is to differentiate the distinct behavioral components of DRL task and correlate the involved neural substrates, which was the theme investigated in the present study. This study first characterized the acquisition process of the DRL-10 sec task into behavioral inhibition and the timing stages, and then assessed the c-Fos levels by immunohistochemistry in the eight brain areas that potentially involved in behavioral inhibition and the timing processes. Regarding the stage of behavioral inhibition, significant increases in c-Fos-positive neurons were observed in the orbitofrontal cortex (OFC), the medial prefrontal cortex (mPFC), and the hippocampal CA1 area. At the stage of the timing being acquired, c-Fos immunohistochemical activity was highly expressed in the anterior cingulated cortex (ACC), OFC, mPFC, the dorsolateral striatum (dlS), the dentate gyrus (DG), and the hippocampal CA1 area. Together, these results showed that the functioning dual paths between the hippocampus CA1 and the prefrontal cortex (OFC and mPFC) are critically essential for developing the appropriate performance via behavioral inhibition in the early-stage of the DRL task and with three other areas (ACC, dlS, and DG) being recruited, an anatomical circuitry connecting prefrontal/striatal/hippocampal structures were involved in the acquisition of interval timing toward the later establishment of the DRL behavior.參考文獻 鄭瑞光（2000）。「大腦多巴胺系統在大鼠操作式制約行為中所扮演的腳色：以時間為主」。未發表之碩士論文，國立政治大學心理系。
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國立政治大學
心理學研究所
94752002
97資料來源 http://thesis.lib.nccu.edu.tw/record/#G0094752002 資料類型 thesis dc.contributor.advisor 廖瑞銘 zh_TW dc.contributor.advisor Liao, Ruey Ming en_US dc.contributor.author (Authors) 鍾居翰 zh_TW dc.contributor.author (Authors) Chung, Chu Hang en_US dc.creator (作者) 鍾居翰 zh_TW dc.creator (作者) Chung, Chu Hang en_US dc.date (日期) 2008 en_US dc.date.accessioned 19-Sep-2009 11:54:33 (UTC+8) - dc.date.available 19-Sep-2009 11:54:33 (UTC+8) - dc.date.issued (上傳時間) 19-Sep-2009 11:54:33 (UTC+8) - dc.identifier (Other Identifiers) G0094752002 en_US dc.identifier.uri (URI) https://nccur.lib.nccu.edu.tw/handle/140.119/37069 - dc.description (描述) 碩士 zh_TW dc.description (描述) 國立政治大學 zh_TW dc.description (描述) 心理學研究所 zh_TW dc.description (描述) 94752002 zh_TW dc.description (描述) 97 zh_TW dc.description.abstract (摘要) 區辨性增強低頻反應作業 (differential reinforcement of low-rate responding task, DRL task) 為一與時間相關聯之操作式制約行為作業，該作業常用於計時行為、行為抑制功能、或抗焦慮與抗憂鬱症等藥物之行為藥理研究的探討。雖然DRL作業是一種實驗室常用的動物行為模式，但是對於上述行為或藥理機制的探討往往缺乏一致性的解釋，其中可能的原因為DRL作業的行為同時包含了計時與行為抑制的成份。針對上述問題，本研究將以DRL行為作業為研究主題，探討作業習得歷程之神經機制。首先根據DRL作業之行為內涵，將作業的習得分為行為抑制與計時先後表現的兩個階段；並依據過去的研究文獻整理出的八個與行為抑制和計時表現相關之大腦區塊，以c-Fos免疫組織化學染色法探討行為抑制和計時的神經機制。實驗結果發現受試於行為抑制的表現階段，其眶眼皮質、內側前額葉皮質、與海馬CA1區域的c-Fos表現量較高；而在計時行為的表現階段，除了和行為抑制有關的三個大腦區塊外，尚有前扣帶迴、紋狀體、與齒狀迴呈現c-Fos表現量增加的現象。綜合以上結果，DRL-10秒作業於學習初期所進行的行為抑制可能和前額葉皮質與海馬體的神經互動有關；而學習較末階段的計時表現，則可能需要前額葉皮質、紋狀體、與海馬等三處較多的次級區域的組織加入，形成神經網路的方式支援之。 zh_TW dc.description.abstract (摘要) Differential reinforcement of low-rate responding (DRL) task was an operant conditioned behavior based on temporal contingency. This task has been widely used to investigate the behavioral components of timing and behavioral inhibition, which is frequently used for pharmacological screening of anxiolytic and antidepressant drugs. Despite of being widely used as an animal behavioral model in the laboratory, but the performance of the DRL task was varied and inconsistent when the drug test conducted. One way to encounter this problematic issue is to differentiate the distinct behavioral components of DRL task and correlate the involved neural substrates, which was the theme investigated in the present study. This study first characterized the acquisition process of the DRL-10 sec task into behavioral inhibition and the timing stages, and then assessed the c-Fos levels by immunohistochemistry in the eight brain areas that potentially involved in behavioral inhibition and the timing processes. Regarding the stage of behavioral inhibition, significant increases in c-Fos-positive neurons were observed in the orbitofrontal cortex (OFC), the medial prefrontal cortex (mPFC), and the hippocampal CA1 area. At the stage of the timing being acquired, c-Fos immunohistochemical activity was highly expressed in the anterior cingulated cortex (ACC), OFC, mPFC, the dorsolateral striatum (dlS), the dentate gyrus (DG), and the hippocampal CA1 area. Together, these results showed that the functioning dual paths between the hippocampus CA1 and the prefrontal cortex (OFC and mPFC) are critically essential for developing the appropriate performance via behavioral inhibition in the early-stage of the DRL task and with three other areas (ACC, dlS, and DG) being recruited, an anatomical circuitry connecting prefrontal/striatal/hippocampal structures were involved in the acquisition of interval timing toward the later establishment of the DRL behavior. en_US dc.description.tableofcontents 中文摘要............................................................i英文摘要............................................................ii第一章 導論........................................................1 引言........................................................1 學習的分子神經機制..........................................2 操作式制約行為作業與早期立即基因之關係......................2 區辨性增強低頻反應作業......................................4 行為抑制/行為衝動之神經機制.................................6 （一）五-色胺酸系統......................................6 （二）海馬迴............................................10 （三）依核核區..........................................11 （四）眶眼皮質..........................................12 （五）額葉—紋狀體神經迴路..............................13 與時間知覺有關的操作式制約行為作業.........................14 （一）高峰時距作業......................................15 （二）時間二分點作業....................................16 時間知覺之相關神經機制.....................................17 （一）多巴胺神經傳導素系統..............................17 （二）皮質—紋狀體神經迴路..............................18 （三）海馬迴............................................20 研究目的及實驗設計.........................................21第二章 實驗材料與方法.............................................24 受試者.....................................................24 實驗儀器...................................................24 操作式壓桿行為訓練之基本實驗程序...........................25 實驗設計及步驟.............................................26 免疫組織化學染色法.........................................28 切片觀察...................................................29 統計方法...................................................29第三章 實驗結果...................................................31實驗一：DRL-10秒作業之行為模式建立........................31實驗二 行為抑制表現相關大腦區塊之c-Fos反應.................31 實驗三 計時表現相關大腦區塊之c-Fos反應.....................33第四章 綜合討論...................................................35一、DRL-10秒作業之行為抑制................................35 （一）眶眼皮質與DRL-10秒作業行為抑制階段之關係........36 （二）內側前額葉皮質與DRL-10秒作業行為抑制階段之關係..37 （三）CA1與DRL-10秒作業行為抑制階段之關係............39（四）其他相關大腦區塊..................................40 （五）小結：行為抑制之神經迴路.........................42二、DRL-10秒作業之計時行為.................................42 （一）計時行為的訊息處理模式...........................43 （二）時鐘歷程.........................................44 （三）記憶歷程.........................................45 （四）決策歷程.........................................47 （五）前扣帶迴、海馬齒狀迴區域、背側側邊紋狀體與計時行為之關連性............................................48 （六）小結：計時之神經機制.............................51三、結論...................................................52參考文獻...........................................................54附圖說明...........................................................76附表：表一至表三...................................................83附圖：圖一至圖三十.................................................85 zh_TW dc.format.extent 96640 bytes - dc.format.extent 121108 bytes - dc.format.extent 134750 bytes - dc.format.extent 269826 bytes - dc.format.extent 236944 bytes - dc.format.extent 128523 bytes - dc.format.extent 217914 bytes - dc.format.extent 221775 bytes - dc.format.extent 182831 bytes - dc.format.extent 104925 bytes - dc.format.extent 4116255 bytes - dc.format.mimetype application/pdf - dc.format.mimetype application/pdf - dc.format.mimetype application/pdf - dc.format.mimetype application/pdf - dc.format.mimetype application/pdf - dc.format.mimetype application/pdf - dc.format.mimetype application/pdf - dc.format.mimetype application/pdf - dc.format.mimetype application/pdf - dc.format.mimetype application/pdf - dc.format.mimetype application/pdf - dc.language.iso en_US - dc.source.uri (資料來源) http://thesis.lib.nccu.edu.tw/record/#G0094752002 en_US dc.subject (關鍵詞) 區辨性增強低頻反應作業 zh_TW dc.subject (關鍵詞) 行為抑制 zh_TW dc.subject (關鍵詞) 計時 zh_TW dc.subject (關鍵詞) 習得歷程 zh_TW dc.subject (關鍵詞) differential reinforcement of low-rate responding task en_US dc.subject (關鍵詞) behavioral inhibition en_US dc.subject (關鍵詞) timing en_US dc.subject (關鍵詞) acquisition en_US dc.subject (關鍵詞) c-Fos en_US dc.title (題名) 時間關聯的操作式制約行為之神經機制：以c-Fos免疫組織化學染色法為例 zh_TW dc.title (題名) Neural mechanisms of the operant conditioned behavior based on temporal contingency: by c-Fos immunohistochemistry en_US dc.type (資料類型) thesis en dc.relation.reference (參考文獻) 鄭瑞光（2000）。「大腦多巴胺系統在大鼠操作式制約行為中所扮演的腳色：以時間為主」。未發表之碩士論文，國立政治大學心理系。 zh_TW dc.relation.reference (參考文獻) Adleman, N. 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