使用錳增強核磁共振顯影探討與學習有關之功能性神經聯結

錳離子在核磁共振顯影中可增強T1權重影像信號，加上其生化特質與鈣離子相似，並且可由鈣離子管道進入神經細胞。由於神經系統沒有代謝錳離子之機制，因此錳離子會順著軸突運輸傳送至軸突末端釋放，再被下一個有活動的細胞吸收。基於上述特質，錳離子可作為顯影劑、神經徑路追蹤劑、以及神經活動標記，通稱為「錳增強核磁共振顯影」。相較於功能性核磁共振顯影，錳增強核磁共振顯影的信號提升率較高，且提供一個能直接追蹤神經活動之方法。本研究企圖將錳增強核磁共振顯影應用於學習與記憶議題上，先於大白鼠顱內注射錳離子，並讓大白鼠在清醒狀態下執行學習作業。假設大白鼠經過學習事件後，神經活動產生改變，其錳離子的吸收與傳送速度會不同於沒有經歷學習經驗的動物，神經活動的差異會顯現於T1權重影像上錳離子的分布範圍與信號強度。實驗一以黑質為測試區域，目的在於找出適合顱內注射的容積，結果發現當錳離子濃度為60 mM時，容積採用63 nl可達到最好效果。實驗二於聚乙烯塑膠管內填入12種濃度之錳離子作為假體插入大白鼠腦中，當錳離子濃度介於50至1000 μM時在T1權重影像中具有信號增強效果。實驗三將錳離子注入杏仁核與海馬，接著讓大白鼠在清醒狀態下進行抑制型逃避學習作業。電擊組的大白鼠在訓練階段接受五次足部電擊（1 mA, 1 s），控制組則否。隔日所取得的影像結果顯示注射於海馬的錳離子會透過穹窿傳至側膈核與韁核，而在杏仁核之錳離子會傳送到終紋床核與黑質。分析各腦區之影像強度，只有終紋床核之亮度在電擊組會顯著低於無電擊組。實驗四中將終紋切斷再於杏仁核注射錳離子，確認累積於杏仁核之錳離子是透過終紋傳至終紋床核。本研究證實錳離子的確可作為神經活動標記，並應用於學習與記憶之動物模型上。未來在影像解析度與分析方法上仍須改進，以增加錳增強核磁共振顯影之可用性。

關鍵字

杏仁核；海馬；終紋床核；側膈核；神經活動標記；抑制型逃避學習作業

並列摘要

Manganese (Mn2+) is used as a contrast agent because it enhances the signal of T1-weighted images in magnetic resonance imaging (MRI). It shares with calcium (Ca2+) certain biochemical properties, and could be taken up by excitable neurons through the calcium channel. No metabolic mechanism washes out Mn2+ accumulated within a neuron, it thus can be transported along the axons, released at the terminal, and taken up by the postsynaptic neuron during excitation. These properties allow Mn2+ to trace fiber track and code the neuronal activity history in the so-called “manganese-enhanced magnetic resonance imaging (MEMRI)”. The present study was aimed to test the hypothesis that the learning-related neuronal activity alters the absorption and transportation rate of Mn2+ in comparison with those without learning, and the difference could be detected by T1-weighted images of MRMRI. The first experiment used the substantia nigra as a testing site for stereotaxic micro-infusion and showed that the optimal dose is 63 nl of 60 mM MnCl2. The second experiment used polyethylene catheters filled with different concentration of manganese inserted into the rat brain as phantom. The signal intensity of those in T1-weighted images was recorded as the concentration varied between 50 to 1000 μM. In the third experiment, male Sprague-Dawley rats received stereotaxic micro-infusion of Mn2+ (60 mM, 63 nl) into the amygdala and hippocampus. After recovery from the anesthesia, the shocked group was subjected to a step-through inhibitory avoidance task with 5 footshocks (1 mA, 1 s). In contrast, the control group was exposed to the same task apparatus but received no footshocks. On the next day, the T1-weighted images were acquired on the Bruker BioSpect 3 T MRI system. The results showed that the manganese infused into hippocampus was transported to the lateral septal nuclei through fornix, and that in amygdala was to bed nucleus of stria terminalis (BNST) and substantia nigra. Only the signal intensity of BNST in the shocked group was significantly lower than the control. After cutting the stria terminalis, manganese was infused into the amygdala in the fourth experiment. The result showed the manganese accumulated in amygdala was transported to BNST through stria ternimalis. The present study proved that Mn2+ could be used as neuronal activity marker in an animal model of learning and memory. However, for this method to be better applied in the future, spatial resolution of images and the analyzing method remain to be improved.

並列關鍵字

amygdala ； hippocampus ； bed nucleus of stria terminalis ； lateral septal nuclei ； neuronal activity history marker ； inhibitory avoidance task

參考文獻

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使用錳增強核磁共振顯影探討與學習有關之功能性神經聯結

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