臺灣博碩士論文加值系統

神經元藉由彼此之間的突觸（Synapse）連結以作訊息溝通。突觸可視為大腦處理訊息的基本單位，因此對於神經元之間突觸形成的研究，在基本機制上甚或病理學的應用上都具有相當的重要性。
在哺乳類動物的中樞神經系統中，最主要的興奮性神經傳導物質是麩胺酸（glutamatic acid）。NMDA和AMPA受器，為最主要的兩種麩胺酸受器，此二受器反應加成，主導一個興奮性突觸反應性質。本論文針對此兩種麩胺酸受器，取胚胎十八天的鼠腦做離體細胞培養，以免疫螢光的方法標定此兩種受器之次級單位，觀察其在神經發育過程中，聚集及分佈的情形。
我們發現，在離體培養一週及兩週時，AMPA受器歷經一次次級單位組成轉變。一週大的麩胺酸突觸上的AMPA受器，以對鈣離子具通透性的亞型為主，發育至兩週大時，AMPA受器轉為以對鈣離子不具通透性的亞型為主。而對於NMDA受器染色則發現，在此時期，NMDA受器由突觸外位置插入突觸膜上。當我們於培養早期以拮抗劑阻斷AMPA受器活性，結果發現NMDA受器得以提早表現於突觸區。
AMPA受器亞型的轉換，會影響細胞內鈣離子的分佈情形。而不同AMPA受器次級單位以及NMDA受器在突觸上表現，皆受鈣離子調節。我們推測神經發育早期藉由AMPA受器亞型轉換，造成胞內局部鈣離子的濃度差異，而此鈣濃度改變調節麩胺酸受器的表現，包括AMPA受器本身次級單位組成，及NMDA插入於突觸區情形。

Neurons connect to each other through synapses. Synapse is the elemental information processing units of the brain. To reveal the mechanism of synaptogenesis is crucial to understand the development of neural circuitry .
A cardinal feature of the formation of synapses is the accumulation of neurotrasmitter receptors at the postsynaptic site. Glutamatergic synapses mediate the main excitatory neural transmission in mammalian CNS. Glutamate receptor clustering in synapses has been studied in culture and slice. Here, I used immunocytochemical methods to investigate the distribution of two main glutamate receptors, AMPA and NMDA receptors, of cultured rat neocortical neurons in various developmentat stages.
We found that between first and second weeks in vitro the subunit compositions of most synaptic AMPA receptors switched from GluR2-free to GluR2-containing receptors. In the same period, more NMDA receptors were recruited from extrasynaptic areas to synapses. We suggest that in the early development stage neurons express mainly Ca++ permeable AMPA receptors at synapses. Ca++ influxes through AMPA receptor may be related to a subtype switch from Ca++ permeable to Ca++ impermeable AMPA receptors and the targeting of NMDA receptors to synapses in the latter stages of development.

壹、緒論……………………………………………………………1
貳、材料與方法……………………………………………………8
一、胚鼠大腦皮質之細胞培養…………………………………9
二、免疫螢光染色……………………………………………..12
參、結果…………………………………………………………..15
肆、討論…………………………………………………………..22
伍、參考文獻……………………………………………………..33
陸、圖……………………………………………………………..39

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