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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 閔明源 | zh_TW |
| dc.contributor.advisor | Ming-Yuan Min | en |
| dc.contributor.author | 詹鎬 | zh_TW |
| dc.contributor.author | Hao Chan | en |
| dc.date.accessioned | 2023-03-19T23:38:48Z | - |
| dc.date.available | 2023-11-10 | - |
| dc.date.copyright | 2022-09-07 | - |
| dc.date.issued | 2022 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | Aghajanian G. K. (1985). Modulation of a transient outward current in serotonergic neurones by alpha 1-adrenoceptors. Nature, 315(6019), 501–503.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/86141 | - |
| dc.description.abstract | 藍斑核為腦中主要正腎上腺素來源，參與如警覺、清醒睡眠等多種反應。藍斑核有著持續、低頻的tonic activity與短暫高頻的phasic activity兩種模式，在近年的研究中發現phasic activity可能參與意識轉移與優化行為表現等複雜認知功能。phasic activity常常由伴隨著一段長時間的抑制(PSI)，可能扮演過濾外界雜訊的功能。關於PSI我們提出三種假說。首先，藍斑核可能釋放正腎上腺素活化自身抑制性α2正腎上腺素受體來造成抑制。其次，藍斑核phasic activity可能活化SK、BK與IK等鈣活化鉀離子通道造成抑制。最後，藍斑核也可能透過以phasic activity刺激週邊抑制性中間神經元來達到對自身進行抑制的現象。實驗中，我們透過腦片電生理的方式紀錄人工誘發phasic-like activity並觀察其後的抑制現象。結果顯示自發tonic activity頻率與PSI持續時間呈現負相關。藥理測驗則顯示α2-正腎上腺素受體抑制劑 (idazoxan)、SK通道抑制劑 (apamin) 與GABAb受體抑制劑 (cgp54626) 皆可縮短PSI持續時間，顯示α2-正腎上腺素受體、SK通道與GABAb受體應皆有參與PSI的產生。 | zh_TW |
| dc.description.abstract | Locus Coeruleus (LC) is the main source of Norepinephrine (NE) in the brain, involving in vigilance, arousal and wake sleep cycle. There are two kinds of firing pattern of LC, continuous low frequency tonic activity and brief high frequency phasic activity. Recent studies have shown that LC phasic activity may participate in complex cognitive function like cognitive shift and optimizing performance. Post stimulation inhibition (PSI) is often observed following phasic activity, which may benefit performance by filtering out distractions. We proposed three possible mechanisms of PSI. First, auto-releasing NE from LC neurons may bind to inhibitory α2-adrenoreceptor (α2-AR) causing PSI. Second, phasic activity may activate calcium-dependent potassium channel (SK, BK and IK channel) causing PSI. Last, LC phasic activity may stimulate surrounding inhibitory interneurons causing PSI. We conduct ex-vivo brain slice electrophysiology on LC neurons, and investigate in mechanism underlying inhibition following manually induced phasic like burst activity. We found that baseline spontaneous firing rate is negatively related to PSI duration, and that α2-AR antagonist idazoxan, SK channel blocker apamin and GABAb receptor blocker cgp54626 could all reduce PSI duration, suggesting that α2-AR, SK channel and GABAb receptor all take part in PSI. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T23:38:48Z (GMT). No. of bitstreams: 1 U0001-0509202218175000.pdf: 1551782 bytes, checksum: bc90d64819127f1f67aafcedaaad2d74 (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 口試委員會審定書 …………………………………………………………………….i
致謝 …………………………………………………………………………………...ii 中文摘要 …………………………………………………………………………….iii Abstract ………………………………………………………………………………iv Content ……………………………………………………………………………….vi Chapter 1. Introduction ………………………………………………………………1 1.1 Locus Coeruleus and Norepinephrine system …………………………………...1 1.2 LC tonic and phasic activity ……………………………………………………..2 1.3 Post stimulation inhibition (PSI) …………………………………………….......3 1.4 Possible mechanisms underlying poststimulation inhibition (PSI) ………………4 1.5 Aim of this study …………………………………………………………………6 Chapter 2. Material and Methods ……………………………………………………7 2.1 Animals ………………………………………………………………………......7 2.2 Acute brain slices preparation ……………………………………………………7 2.3 Electrophysiologic experiments …………………………………………………8 2.4 PSI duration measurement …………………………………………………….....9 2.5 Optogenetic induced outward current …………………………………………..11 2.6 Immunohistochemistry (IHC) staining …………………………………………11 2.7 Data analysis ……………………………………………………………………12 Chapter 3. Result …………………………………………………………………….13 3.1 Baseline activity and PSI duration ……………………………………………...13 3.2 PSI duration of optogenetic and I-injection induced burst ……………………...14 3.3 Effects of α2-AR on PSI : idazoxan decrease PSI duration ……………………..16 3.4 Effects of extracellular calcium concentration on PSI ………………………….17 3.5 Effects of Kca channels on PSI : apamin decrease PSI duration ………………...18 3.5.1 Whole-cell recording with 2 mM EGTA internal buffer …………………..18 3.5.2 Extracellular attach recording ……………………………………………...19 3.5.3 Whole cell recoding with 0.1 mM EGTA internal ………………………….20 3.6 Effects of GABAb receptor on PSI : cgp54626 decrease PSI duration …………21 3.7 Summary ………………………………………………………………………...21 Chapter 4. Discussion ………………………………………………………………...22 4.1 Experimental limitations ………………………………………………………...22 4.1.1 Norepinephrine supply in acute slices ……………………………………...22 4.1.2 Induced burst activity vs spontaneous phasic activity ……………………...23 4.1.3 optogenetic stimulation ……………………………………………………..23 4.2 Inhibition between LC neurons …………………………………………………24 4.2.1 Efferent subpopulation of LC ………………………………………………24 4.2.2 Lateral inhibition on non-phasic LC neurons ………………………………24 Chapter 5. Reference …………………………………………………………………26 Chapter 6. Figures ……………………………………………………………………33 Figure 1. PSI duration testing set up ………………………………………………...33 Figure 2. PSI duration under different baseline activity …………………………….34 Figure 3. Optogenetic stimulation on driven and non-driven neurons ……………..35 Figure 4. Effects of idazoxan on PSI of I-injection or optogenetic induced burst …...36 Figure 5. Outward current following optogenetic stimulation ……………………...37 Figure 6. Effects of low aCSF Calcium concentration on PSI ………………………...38 Figure 7. Effects of KCa channel blockers on PSI …………………………………...39 Figure 8. Effects of KCa channel blockers on PSI (cell-attach recording) …………..41 Figure 9. Effects of KCa channel blockers on PSI (low EGTA) ……………………..43 Figure 10. Effects of GABAb blocker on PSI ………………………………………….44 Figure 11. Correlation of PSI duration with baseline activity and burst activity ……45 | - |
| dc.language.iso | zh_TW | - |
| dc.title | 藍斑核活化後長抑制反應機制探討 | zh_TW |
| dc.title | Investigation of mechanisms underlying post-stimulation inhibition in locus coeruleus | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 110-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.author-orcid | 0000-0001-9771-1869 | |
| dc.contributor.oralexamcommittee | 陳示國;徐經倫;楊琇雯 | zh_TW |
| dc.contributor.oralexamcommittee | Shih-Kuo Chen;Ching-Lung Hsu;Hsiu-Wen Yan | en |
| dc.subject.keyword | 藍斑核,正腎上腺素,抑制性中間神經元,鈣活化鉀離子通道,phasic反應, | zh_TW |
| dc.subject.keyword | locus coeruleus,Norepinephrine,inhibitory interneuron,Calcium dependent potassium channel,phasic activity, | en |
| dc.relation.page | 45 | - |
| dc.identifier.doi | 10.6342/NTU202203169 | - |
| dc.rights.note | 同意授權(全球公開) | - |
| dc.date.accepted | 2022-09-07 | - |
| dc.contributor.author-college | 生命科學院 | - |
| dc.contributor.author-dept | 生命科學系 | - |
| dc.date.embargo-lift | 2025-09-01 | - |
| 顯示於系所單位： | 生命科學系 | |
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