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研究生:葉韋均
研究生(外文):Wei-Chun Yeh
論文名稱:蕈膽鹼對於海馬迴齒狀迴區域中高頻動作電位籃狀細胞之興奮性影響
論文名稱(外文):Muscarinic excitation of fast-spiking basket cells of rat hippocampal dentate gyrus
指導教授:連正章
指導教授(外文):Cheng-Chang Lien
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:神經科學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:35
中文關鍵詞:海馬迴齒狀迴籃狀細胞蕈膽鹼
外文關鍵詞:hippocampusdentate gyrusbasket cellsmuscarine
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大鼠腦中乙醯膽鹼的傳遞系統,與在學習和記憶時所產生的腦波有密切關聯;其腦波頻率主要落於θ (4-10 Hz) 與γ (30-100 Hz) 之範圍。前人研究指出,能產生高頻動作電位的籃狀細胞 (fast-spiking basket cells) 為調控γ頻率腦波的基本要素;此類細胞在新皮質中,對乙醯膽鹼的感受性卻相當低,而在海馬迴CA1區域的細胞反應則尚未被研究。在海馬迴中,齒狀迴區域被視為獨立的振盪器(oscillator),與腦波之產生有密切關聯,然而齒狀迴區域籃狀細胞對乙醯膽鹼之藥理學反應卻尚未被研究。此研究主要對這個區域產生高頻動作電位的籃狀細胞所表現的一種乙醯膽鹼接受器--蕈毒鹼接受器(Muscarinic receptor),活化後所產生的反應。取大鼠的腦組織切片,以全細胞記錄(whole-cell recording)的方式來研究。實驗分別在室溫與接近大鼠體溫的狀況下進行,於記錄槽中以高壓氧(95% O2/5% CO2)持續灌注的人工腦脊髓液灌流,同時加入離子通道型谷胺酸鹽接受器(ionotropic glutamate receptor)與A型γ胺基丁酸接受器(GABAA receptor)的抑制劑,阻斷其他化學傳遞物影響。在加入蕈膽鹼後,細胞被去極化,接著產生頻率介於θ與γ頻率的動作電位。以電位拑制記錄(voltage-clamp recording)的方式,能觀察到細胞的靜止電流減少,所減少的電流反轉電位接近於鉀離子通道的平衡電位,而且這樣的反應可以被M1亞型的蕈膽鹼接受器拮抗物 (Pirenzepine) 所回復,意味著蕈膽鹼藉由活化M1亞型的蕈膽鹼接受器,進而抑制鉀離子通道的開啟,造成細胞去極化。由以上的結果可知,在海馬迴齒狀迴區域中產生高頻率動作電位之籃狀細胞,其表面的蕈膽鹼接受器被活化後,可驅使海馬迴中γ頻率腦波的產生,進而放大腦皮質的功能。
Cholinergic transmission is involved in learning- and memory-associated theta (4-10 Hz) -gamma (30-100Hz) oscillations. Although fast-spiking basket cells (BCs) are suggested to be the cellular substrate of gamma oscillations, accumulating studies showed that fast-spiking BCs in the neocortex are unresponsive to cholinergic modulation. In contrast to neocortex, cholinergic effects on fast-spiking BCs in the hippocampus CA1 region have remained elusive. Dentate gyrus is one of gamma oscillators in the hippocampus. In contrast to the neocortex and the CA1 region, the impacts of mAChR activation on excitatory and inhibitory outputs of fast-spiking BCs in the dentate gyrus remain unexplored. Here this study investigated the influence of postsynaptic muscarinic acetylcholine receptor (mAChR) activation on fast-spiking BCs in the dentate gyrus of rat brain slices using patch-clamp whole cell recording. Bath application of mAChR agonist muscarine in the presence of ionotropic glutamate receptor and GABAA receptor blockers strongly depolarized fast-spiking BCs and led them to fire in the theta to gamma range at room temperature and body temperature. In voltage-clamp recording, mAChR activation markedly reduced resting current, which exhibited a reversal potential close to the equilibrium potential for K+ channels. Furthermore, the effect was largely reversed by pirenzepine, the M1 subtype muscarine receptor selective antagonist, suggesting that inhibition of K+ current was mediated through activation of postsynaptic M1 subtype muscarinic receptors. The functional consequences of muscarinic excitation on BCs may provide driving force for these neurons to generate gamma rhythm and thereby enhance cortical performance.
Abstract in Chinese______________________________________ii
Abstract in English______________________________________iii
Introduction_____________________________________________1
Materials and methods____________________________________4
Preparation of hippocampal slices_______________________4
Electrophysiology_______________________________________4
Solutions and drugs_____________________________________5
Post hoc identification of BC morphology________________5
Data analysis and statistics____________________________6
Results__________________________________________________8
Morphological identification of fast-spiking BCs________8
Activation of mAChRs influenced AP initiation of BCs____9
Activation of mAChRs induced depolarization of BCs______9
Activation of mAChRs reduced resting conductance of BCs_11
M1 subtype mAChR activation decrease K+ conductances____12
Discussion_______________________________________________14
Selectivity in cholinergic neuromodulation of interneuron subtypes_________________________________________________14
Muscarinic receptors mediated depolarizing response is through inhibition of K+ conductances____________________15
Functional significance of muscarinic excitation________17
References_______________________________________________18
Figures__________________________________________________24
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