藍斑核活化後長抑制反應機制探討

Investigation of mechanisms underlying post-stimulation inhibition in locus coeruleus

詹鎬(Hao Chan)

指導教授 ： 閔明源

國立臺灣大學/生命科學院/生命科學系/碩士(2022年)

https://doi.org/10.6342/NTU202203169

摘要

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。

關鍵字

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

並列摘要

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.

並列關鍵字

locus coeruleus ； Norepinephrine ； inhibitory interneuron ； Calcium dependent potassium channel ； phasic activity

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