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標題: | 多巴胺及乙醯膽鹼對視丘下核到外側和內側蒼白球麩胺酸突觸傳導之修飾作用 Dopaminergic and cholinergic modulation of subthalamopallidal glutamatergic synaptic transmission |
作者: | Yin-Chieh Chen 陳映潔 |
指導教授: | 郭鐘金(Chung-Chin Kuo) |
關鍵字: | 視丘下核,外側蒼白球,內側蒼白球,突觸傳遞,電生理, subthalamic nucleus,external globus pallidus,internal globus pallidus,synaptic transmission,electrophysiology, |
出版年 : | 2019 |
學位: | 碩士 |
摘要: | 基底核(basal ganglia)藉由錯綜複雜的神經網路系統與大腦皮層(cortex)做連結,由數個腦核區所組成,包含紋狀體(striatum)、視丘下核(subthalamic neucleus)、蒼白球(globus pallidus)及黑質(substantia nigra)。其主要的功能為人體運動的控制,並且在認知、行為、情感等方面上也扮演一重要的角色。而在基底核內部的神經網路可以分為直接迴路、間接迴路與超直接迴路。本篇主要探討各種神經調控物質(neuromodulator)在基底核的輸出核區:STN對外側蒼白球與內側蒼白球的調控作用。我們使用C57BL/6 mice製作大腦切片進行實驗,在視丘下核處給予電刺激,並且在小鼠的蒼白球進行whole-cell voltage clamp,分別記錄外側蒼白球與內側蒼白球的AMPAR glutamate ligand-gated channel的電流,並且加入acetylcholine、dopamine等神經修飾物質之致效劑與拮抗劑的方式,來觀察藥物對此突觸訊息傳遞之影響效果。研究結果顯示,當我們給予pair-pulse電刺激(間隔分別為100、50、20 ms,亦即約當10、20、50 Hz之刺激)時,在加入A68930 (D1 agonist)時,GPe和GPi的AMPA電流在第一下刺激(P1)的電流大小與PPR皆沒有顯著影響。同樣地用SKF83566 (D1 antagonist)檢測時,對GPe和GPi的P1大小與PPR也沒有顯著影響。而加入Quinpirole (D2 agonist)後,對GPe和GPi的P1電流皆下降2到3成,但對PPR則產生上升的趨勢。給予Eticlopride (D2 antagonist),對GPe和GPi的P1電流與PPR皆沒有顯著影響。在acetylcholine實驗中,我們發現加入carbachol (cholinergic agonist)時,對GPi做連續五下的電刺激,10、20、50 Hz等3個頻率組別的P1電流皆下降4成,且PPR皆稍微上升,但沒有上升到產生顯著差異;另外P5/P1 ratio也有上升的趨勢,但僅10 Hz、20 Hz組別上升達顯著差異(control組各為0.76、0.73,給予carbachol後約各為0.85、0.89)。另一方面,加入nicotine後,對GPe和GPi的P1大小與PPR皆沒有顯著影響,但在加入mecamylamine (nicotinic antagonist)後GPe和GPi的PPR有些微上升的趨勢,但不影響P1電流大小。然而在加入muscarine後,GPe和GPi的P1電流皆顯著下降6~7成,且PPR皆有稍微上升的現象。這些結果顯示,acetylcholine對視丘下核到GPe、GPi的glutamatergic有顯著調控突觸電流的功能,並且,在我們的實驗條件下發現可能是經由muscarine受體去作修飾調控。 The basal ganglia are comprised of striatum, subthalamic nucleus (STN), globus pallidum and substantia nigra. They work in concert with the cortex, thalamus, and brain stem and play an important role in many different functions, including voluntary motor control, cognitive, behavior, and emotional functions. The cortico-subcortical re-entrant loops always involve basal ganglia, and can be divided into direct, indirect and hyperdirect pathways. We endeavored to investigate the effect of different neuromodulators on the Glutamatergic synaptic transmission from STN to GPe and STN to GPi, and evoked excitatory postsynaptic currents (EPSCs) separately from STN to GPe and STN to GPi in C57BL/6 mouse brain slices with whole-cell voltage-clamp technique. Pair pulse stimuli in 3 different frequencies (10、20 and 50 Hz) were applied to the STN to GPe and STN to GPi fibers, respectively, to evoke EPSCs. We found that D1 agonist (A68930) has no apparent effect on P1 amplitude and PPR in both STN-GPe and STN-GPi synaptic transmission. D1 antagonist (SKF83566) affects neither P1 amplitude nor PPR in both STN-GPe and STN-GPi. D2 agonist (Quinpirole) decreases P1 amplitude by 20~30% and slightly increases PPR in both STN-GPe and STN-GPi pathway. D2 antagonist (Eticlopride) affects neither P1 amplitude nor PPR of STN-GPe and STN-GPi. We also examined the effect of acetylcholine modulated STN-GPe and STN-GPi synaptic transmission. With a 5-pulse stimulation protocol in GPi, we found that carbachol markedly decreases P1 amplitude and slightly increases both P2/P1 and P5/P1 ratios in STN-GPi. While nicotine has no effect on both P1 amplitude and PPR in STN-GPe and STN-GPi, nicotine antagonist (mecamylamine) shows a tendency to increase PPR in both STN-GPe and STN-GPi but causes no change to P1 amplitude. Muscarine significantly decreases P1 amplitude by 60~70% and slightiy increases PPR in both STN-GPe and STN-GPi. We therefore conclude that both STN-GPe and STN-GPi AMPAergic transmissions are significantly modulated by acetylcholine via muscarinic receptor and slightly modulated by dopamine via dopamine D2 receptor. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/71466 |
DOI: | 10.6342/NTU201900474 |
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顯示於系所單位: | 生理學科所 |
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