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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鍾居翰, Chung, Chu Hang Unknown Date (has links)
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.
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