在過去的文獻中指出，齧齒類動物的內側眼窩額葉皮質主動的參與在獎賞類的決策行為之中，內側眼窩額葉皮質有神經投射到各個組成恐懼迴路的腦區，其中包含杏仁核、內側前額葉、以及海馬迴，這幾個腦區在恐懼制約及消除行為中都佔有相當重要的角色。在我們實驗室先前的實驗中，我們發現活化外側眼窩額葉皮質會干擾恐懼消除的學習，在這個實驗中，我們則要研究活化內側眼窩額葉皮質對於恐懼迴路以及恐懼消除記憶的影響。
我們的行為程序是三天的帕夫洛夫恐懼制約及消除實驗，其中以大鼠的靜止作為恐懼反應的指標，並在各個階段進行記錄。在第一天，所有的大鼠都會接受聲音與電擊的配對，在第二天，半數的動物接受恐懼消除實驗，另外半數則不做特別處置，在第三天，所有的動物都會接受聲音刺激以的測試其恐懼記憶的形成。 內側眼窩額葉皮質會在三個不同的時間點接受N-甲基-D-天門冬胺酸的活化或是生理食鹽水作為控制組，三個時間點分別為:恐懼消除記憶的形成、固化、以及提取階段。
我們的實驗結果顯示，在執行恐懼記憶消除實驗之前活化內側眼窩額葉皮質會完全阻礙恐懼消除記憶的形成，但在執行恐懼記憶消除實驗之後活化內側眼窩額葉皮質則對恐懼消除記憶的固化沒有影響。在測試階段之前活化內側眼窩額葉皮質對恐懼消除記憶的提取影響則未明，由於測試時的行為受到藥物的直接影響，動物的恐懼反應皆隨著時間由低向高逐漸攀升，故無法用來判斷記憶的提取與否。綜合上述結果，我們結論內側眼窩額葉皮質在恐懼記憶消除的過程中扮演重要的調控角色。

The medial orbitofrontal cortex (mOFC) in rodent has been shown to be involved in the reward-based decision-making process. The mOFC sends projections to several brain areas of the fear circuit, including the amygdala, the medial prefrontal cortex (mPFC), and the hippocampus (HPC), which are important for fear learning as well as extinction. In our previous studies, we reported that the activation of lateral orbitofrontal cortex (lOFC) interferes with extinction learning. In this study, we are interested in the regulation of the mOFC on the fear circuit and fear extinction memory.
We used a 3-Day Pavlovian fear conditioning and extinction protocol and recorded the learned fear measured by freezing level during each behavioral phase. On Day 1, all rats were conditioned with the tone-footshock pairs. On Day 2, the rats underwent the extinction (tone) or exposure (no tone) procedure. On Day 3, all rats were presented with tones to test their memory of fear extinction. The mOFC was activated with N-methyl-D-acidic acid (NMDA) or saline (control group) through the pre-implanted cannula at three different time points: the acquisition, consolidation, or retrieval phase of extinction.
Our results suggested that pre-extinction activation of the mOFC abolished the acquisition of fear extinction, while post-extinction activation of the mOFC had no effects on consolidation of extinction memory. The effects of pre-test activation of the mOFC cannot be concluded since the deviation in behavior could result from either the alternation in fear expression and/or memory retrieval. Furthermore, there were similar patterns of behavioral change under the effects of the drug, where the freezing levels were low in the early trials and increased gradually. Together, our results indicated that the mOFC is critically involved in the regulation of fear extinction memory.

中文摘要 1
Abstract 2
致謝 3
Table of content 4
Introduction 5
Materials and Methods 9
Subjects 9 Surgery 9
Experimental Design 9 Apparatus 10
Behavioral procedures and pharmacology 10
Drug infusion 10
Histology 11
Data analysis 11
Results 12
Experiment 1: Pre-EXT mOFC activation on acquisition of fear extinction 12
Experiment 2: Post-EXT mOFC activation on consolidation of fear extinction 13
Experiment 3: Pre-TEST mOFC activation on retrieval of fear extinction 14
Discussion 16
Reference 20
Figures 24

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