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標題: | 神經調控物質對視丘下核到內側蒼白球興奮性突觸傳導之作用 Modulation of the excitatory synaptic transmission from subthalamus to globus pallidus pars internus (endopeduncular nucleus) |
作者: | Wei-Ya Chen 陳薇雅 |
指導教授: | 郭鐘金(Chung-Chin Kuo) |
關鍵字: | 視丘下核,內側蒼白球, subthalamic neucleus,globus pallidus interna, |
出版年 : | 2014 |
學位: | 碩士 |
摘要: | 視丘下核(Subthalamic neucleus,STN)與內側蒼白球(Globus pallidus interna,GPi)都位於大腦中的基底核(Basal ganglia),而基底核由許多不同的核區所組成,其主要的功能為控制生物體的自主運動。另外,基底核同時也參與了記憶、情感等認知行為。其中在indirect pathway中視丘下核會釋放興奮性的glutamate去調控內側蒼白球,而glutamate會開啟位在後突觸細胞上的AMPA及NMDA這兩種ligand-gated receptor。又因內側蒼白球並非只會接受來自視丘下核的刺激,而亦具有其他種類之神經傳遞物質的接受器,故本研究將會針對不同的神經傳遞物質對於此傳遞路徑的影響進行探討。在本研究中,我們利用C57B/L6 mice的大腦切片來進行實驗。首先我們在視丘下核給予電刺激,並在後突觸的entopeduncular nucleus (EP)(齧齒類腦中內側蒼白球的同源構造)使用whole cell voltage-clamp的方式,分別記錄AMPA和NMDA兩種離子通道開啟時所產生的電流。並且,以外加acetylcholine、dopamine、serotonin、norepinephrine等神經傳遞物質的方式,來探討這些神經傳遞物質對此條路徑的傳導性質有何影響。研究結果顯示當我們進行成對刺激(以20 Hz的頻率,給予兩次刺激),以及80 Hz的頻率給予連續五下刺激兩種刺激模式時,外加cholinergic agonist (carbachol),不論是NMDA或是AMPA的電流,其對第一個刺激之反應(P1)大小都會被顯著的抑制。而對第二個刺激之反應(P2)則被抑制的程度較低,因此P2/P1比值(paired pulse ratio, PPR)皆會上升。當分別給予muscarine和nicotine時,miscarine對突觸電流的效果與carbachol相似。另外在80 Hz連續五下的刺激條件下,可以看出muscarine對P1的抑制效果最好,而對P2~P5的抑制則較弱,P2/P1以及P5/P1都有上升的趨勢。而nicotine沒有顯著的效果,因此acetylcholine在本系統應是作用在muscarinic receptor上。在dopamine的實驗中,D1 agonist(A-68930)對這段路徑沒有顯著性的影響,而D2 agonist(quinpirole)則對AMPA電流有輕微的抑制效果,且會造成PPR的上升,但對80 Hz刺激下的電流大小影響程度較低。Serotonin agonist (5-CT)同樣對本段路徑的AMPA電流有抑制的效果,但不會造成PPR的上升,另一方面5-CT對NMDA電流則沒有明顯的影響,在80 Hz的刺激頻率下也可得到類似的結果。至於norepinephrine 對於這個系統並沒有顯著性的作用。我們因此結論,在視丘下核到內側蒼白球的這段路徑上,acetylcholine、dopamine、serotonin都具有調控突觸電流的功能。且這些神經調控物質對於突觸電流的調控方式各有不同,因此藉由不同神經調控物質之間的配合,生物體可適應各種不同的需求。而當神經傳遞物質失調時,即有可能造成神經性疾病的發生。 Subthalamic neucleus (STN) and internal segment of globus pallidus (GPi) are parts of the basal ganglia, which are composed of quite a few different nuclei. The major function of basal ganglia is contributory to the control of voluntary motor behavior and cognitive processes. The pathway from STN to GPi is glutamatergic. Glutamate open two different ligand-gated, namely AMPA and NMDA receptor, channels. In addition to glutamate receptor, GPi contains other neurotransmitter and neuromodulator receptors. The purpose of this research is to investigate the effect of different neuromodulator on the glutamatergic transmission from STN to GPi. We recorded the evoked excitatory postsynaptic currents (eEPSCs) from endopeduncular nucleus (EP, the homolog of GPi in rodent) in C57B/L6 mice brain slices with whole-cell voltage-clamp technique. Two different protocols were used, one is pair-pulse stimulation (two stimuli were given in an interval of 50ms), and the second is five stimuli in a train with 80 Hz frequency. Neuromodulators such as acetylcholine, dopamine, serotonin and norepinephrine, are added to the excellular solution to investigate their effect on the STN-EP synaptic transmission. We found that cholinergic agonist (carbachol) markedly reduces the response to the first stimulus (P1) for both AMPA and NMDA currents, but the effect on the response to the second stimulus (P2) is smaller. The ratio between P2 and P1 (P2/P1 or paired-pulse ratio, PPR) therefore significantly increases. The effect of carbachol could be mimicked by muscarinic, but not nicotinic agonists. We found that when the 80 Hz stimulation protocol is used, muscarine inhibits P1 currents with a higher percentage than P2~P5 currents. Therefore, the ratio of P2/P1 and P5/P1 increases. D1-agonist (A-68930) has no apparently effect on this synaptic transmission. In contrast, D2-agonist (quinpirole) could inhibit AMPA currents yet increase PPR slightly. But quinpirole has a smaller influence on AMPA currents with 80 Hz stimulation. On the other hand, serotonin agonist (5-CT) inhibits AMPA currents markedly, but has no effect on either AMPA PPR or the amplitude of NMDA currents. The results of using 80 Hz protocol is similar to 20 Hz protocol above. Norepinephrine, as a neuromodulator for many systems in brain, has no discernible effect on either current amplitude or PPR in the STN-EP glutamatergic neurotransmission. We conclude that acetylcholine, dopamine and serotonin could modulate the STN-EP synaptic transmission by different mechanisms, orchestrating a basis for the adjustment of the movement mode for different conditions. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/55426 |
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