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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 郭鐘金 | |
dc.contributor.author | Yu-Ting Chen | en |
dc.contributor.author | 陳瑜庭 | zh_TW |
dc.date.accessioned | 2021-06-15T11:21:01Z | - |
dc.date.available | 2018-08-26 | |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-19 | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49255 | - |
dc.description.abstract | The basal ganglia are comprised of the striatum, the globus pallidus, the subthalamic nucleus, and the substantia nigra. They participate in a variety of functions including: voluntary motor control, procedural learning, eye movement, cognitive and emotional functions. Because basal ganglia dysfunctions often lead to a wide spectrum of motor deficits, they are generally considered to be motor structures. It is well known that the functions of the basal ganglia are markedly modulated by different neuromodulators, and disturbances of these modulations may be related to diseases such as Parkinson’s disease (PD). The external globus pallidus (GPe) and the subthalamic nucleus (STN) are classically viewed as part of the indirect pathway. They are reciprocally connected and serve as a putative generator of pathological semi-rhythmic burst firings in PD. The aim of this research is to investigate the effect of different neuromodulators on the GABAergic synaptic transmission from GPe to STN. We recorded evoked inhibitory postsynaptic currents (eIPSCs) from GPe to STN in C57BL/6 mouse brain slices using whole-cell voltage-clamp technique. We gave trains of stimuli (5 pulses in a train) at three different frequencies (8 Hz, 20 Hz, and 80 Hz), attempting to simulate the spontaneous firing rates of GPe neurons of rodents. We found that cholinergic agonist (carbachol) markedly reduced the P1 amplitude of GABAergic eIPSCs and showed a tendency to increase both P2/P1 and P5/P1 ratios. The inhibitory effect of carbachol could be mimicked by muscarinic but not nicotinic agonists. Moreover, the modulatory effect of carbachol on GABAergic eIPSCs persisted in the presence of nicotinic antagonist (mecamylamine). To clarify the muscarinic subtype(s) involved, we further examined the effect of M1 agonist (cevimeline) and M2 agonist (arecaidine). We found that cevimeline had no apparent effect on GPe-STN synaptic transmission, while arecaidine exhibited inhibitory actions on synaptic currents in a concentration-dependent manner. In addition, M2 antagonist (AQ-RA 741) totally abolished the effect of carbachol. We also examined whether the dopamine system modulated GPe-STN synaptic transmission. D1 agonist (A68930) did not affect either the amplitude or the P2/P1 and P5/P1 ratios of GPe-STN synaptic currents. On the contrary, D2 agonist (B-HT 920) slightly increased the amplitude of GABAergic eIPSCs but had inconsistent effects on P2/P1 and P5/P1 ratios. However, D2 antagonists (eticlopride and L-741,626) alone failed to affect GPe-STN synaptic transmission. On the other hand, norepinephrine slightly boosted the amplitude of eIPSCs but did not affect either the P2/P1 or the P5/P1 ratio. Serotonergic agonist (5-CT) significantly decreased the amplitude of eIPSCs at relatively high concentrations with a tendency to increase the P2/P1 and P5/P1 ratios. We conclude that acetylcholine and serotonin could modulate the GPe-STN synaptic transmission. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T11:21:01Z (GMT). No. of bitstreams: 1 ntu-105-R02441015-1.pdf: 2622089 bytes, checksum: c30acbbd3748685ea91c9989377f0a8f (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 口試委員會審定書 #
誌謝 i 中文摘要 ii 英文摘要 iv 目錄 vi 圖目錄 ix 第一章 導論 1 1.1 基底核(basal ganglia) 1 1.1.1 基底核中的神經傳導路徑 1 1.1.2 基底核中主要幾個核區的性質 4 1.2 視丘下核的神經連結 7 1.2.1 傳入視丘下核的連結 (Afferent connections) 8 1.2.2 由視丘下核傳出的連結 (Efferent connections) 9 1.2.3 外側蒼白球傳入視丘下核連結的重要性 9 1.3 突觸可塑性對突觸訊息傳遞的影響 10 1.3.1 造成synaptic depression的可能機制 10 1.3.2 造成synaptic facilitation的可能機制 12 1.4 外側蒼白球與視丘下核上的受體 13 1.4.1 外側蒼白球投射神經元所表現的受體 13 1.4.2 視丘下核投射神經元所表現的受體 13 1.5 受體的生理功能 13 1.5.1 乙醯膽鹼(Acetylcholine) 14 1.5.2 多巴胺(Dopamine) 16 1.5.3 正腎上腺素(Norepinephrine) 18 1.5.4 血清素(Serotonin) 20 1.6 外側蒼白球與視丘下核在疾病病態生理以及疾病治療上所扮演的角色 21 第二章 材料與方法 25 2.1 實驗動物 25 2.2 腦切片的製備 25 2.3 玻璃電極的製備 26 2.4 壓片器 26 2.5 細胞電生理紀錄以及電刺激 26 2.6 藥品 27 2.7 數據取得與分析 31 第三章 結果 32 3.1 GPe-STN GABAergic突觸電流 32 3.2 Carbachol對GPe-STN突觸電流有抑制性的作用 32 3.3 Nicotine對GPe-STN突觸電流沒有顯著的影響 33 3.4 Muscarine對GPe-STN突觸電流有抑制性的作用 34 3.5 不同cholinergic agonists對GPe-STN電流的影響程度 34 3.6 M1 receptor活化對於GPe-STN突觸電流並無顯著效果 35 3.7 CCh很有可能係透過M2 receptor來調控GPe-STN突觸電流 36 3.8 A68930對GPe-STN突觸電流無顯著影響 37 3.9 B-HT 920對GPe-STN突觸電流有輕微的促進作用 37 3.10 D2 antagonist對GPe-STN突觸電流無顯著影響 37 3.11 Norepinephrine對GPe-STN突觸電流有輕微的促進作用 38 3.12 5-CT對GPe-STN突觸電流有抑制性的作用 39 第四章 討論 40 4.1 Acetylcholine的調控功能 41 4.2 Dopamine的調控功能 45 4.3 Norepinephrine的調控功能 49 4.4 Serotonin的調控功能 51 4.5 神經調控因子對本段路徑的調控結果所可能具有之生理以及病態生理意義 53 第五章 參考資料 89 | |
dc.language.iso | zh-TW | |
dc.title | 乙醯膽鹼及血清素對外側蒼白球至視丘下核群聚性突觸傳導的調控作用 | zh_TW |
dc.title | Cholinergic and serotonergic modulation of trains of synaptic transmission from external globus pallidus to subthalamic nucleus | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 黃榮棋,楊雅晴 | |
dc.subject.keyword | 基底核,視丘下核,外側蒼白球,神經調控物質,突觸可塑性, | zh_TW |
dc.subject.keyword | basal ganglia,subthalamic nucleus,external globus pallidus,neuromodulator,synaptic plasticity, | en |
dc.relation.page | 116 | |
dc.identifier.doi | 10.6342/NTU201603415 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2016-08-19 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生理學研究所 | zh_TW |
顯示於系所單位: | 生理學科所 |
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