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標題: | 瞬變型鈣離子通道對視丘腹側核和網狀核神經元放電模式與交互活動的影響 Involvement of the T-type Calcium channel in discharge pattern and interaction of ventral posterior and reticular thalamic neurons |
作者: | Yi-Fang Liao 廖儀芳 |
指導教授: | 嚴震東(Cheng-Tung Yen) |
關鍵字: | T通道, T-channel, |
出版年 : | 2011 |
學位: | 博士 |
摘要: | T-type Ca2+ channel (T-channel)是引起視丘神經元bursting放電的關鍵離子通道。其亞型Cav3.1在視丘腹尾核區ventral posterior thalamic nucleus (VP),及Cav3.2和Cav3.3在視丘網狀核區(Reticular thalamic nucleus, RT)的表現並具有組織專一性的特徵。近來研究發現在疼痛刺激下的行為反應在Cav3.1基因缺失( knock out, KO)小鼠有增加情形,而在Cav3.2 KO則是減少。VP是體感覺訊息傳遞上重要的傳遞者,而與其密集相互投射的抑制性RT神經元均利用bursting做為主要的放電模式之一。因此,在實驗中同時記錄此二核區的神經元放電可幫助了解T-channel變異所造成的神經元bursting的變化。
利用多通道單一神經元胞外記錄方式,我們同步記錄麻醉下Cav3.1和Cav3.2 KO小鼠VP和RT的神經元活性。在第一部分的結果主要是在比較此兩種T-channel KO小鼠VP和RT神經元在自發性活性的差異。我們發現,在VP核區中僅有1%體感覺神經元與痛覺相關;在RT則多達50%,同時這個比例在Cav3.2 KO明顯減少。Bursting在Cav3.1VP幾乎消失的結果是與前人一致的。在Cav3.2 KO則是看到不僅RT bursting減少並且bursting強度明顯衰弱,同時還發現Cav3.2 KO的VP burst活性增加。 目前很少研究探討視丘對傷害與非傷害性刺激時反應的放電模式特別是反應模式與爆裂式放電的關係。因此,本論文第二部分利用Cav3.1 和Cav3.2這兩種在VP和RT具有專一性表現的小鼠觀察burst firing受影響後,對刺激的反應的變化。我們發現在正常小鼠中,非傷害性刺激在視丘VP和RT引起以burst firing 為主的反應形式,而傷害性刺激則引起單一動作電位的反應。此現象在T-channel KO小鼠也可觀察到,但在Cav3.1 KO VP對非傷害性的刺激,burst firing的比例顯著低於正常小鼠而其RT以單一動作電位反應傷害性刺激的表現更顯著。在Cav3.2 KO,VP 和 RT burst firing對非傷害性物的物理性刺激的反應則是減少。Cav3.2 KO burst firing在由雷射熱痛引發的反應中,表現較少burst firing且強度也較低。另外,Cav3.2 VP和RT對雷射和電刺激的反應延遲時間都較正常鼠長。 本研究最後一部分比較了視丘內部神經元在較長時間的交互活動。我們發現視丘神經元具有一個共同漲落的慢周期變化。而這個週期性變化在VP和RT中呈現此消彼長相反的活性。這個震盪中神經元間彼此的關連性在Cav3.1和Cav3.2都較為減弱。 綜合以上結果,我們認為T-channel參與了視丘VP和RT的節律性活性。而此視丘的節律性活性變化可能對T-channel缺失的小鼠在疼痛行為上的表現有貢獻。 Low-threshold T-type calcium channels (T-channels) are critically important in the generation of thalamic burst activities. Different subtypes of T-channel distributed differentially in thalamic ventroposterior nucleus (VP, Cav3.1) and reticular thalamic nucleus (RT, Cav3.2 and Cav3.3). Furthermore, T-channel knockout (KO) mice showed contrast nociceptive behaviors, such that an increase was seen in Cav3.1 KO and a decrease in Cav3.2 KO. Considering the important role in sensory relay function of VP neuron and it’s densely reciprocal connection to GABAergic RT, it is important to examine VP and RT neurons simultaneous and compare their bursting activity in the T-channel KO mice. We used multi-channel single-unit recording method to study the changes in the firing property of VP and RT neurons in Cav3.1 and 3.2 KO mice in the anesthetized condition. In the first part of this study, we compared the spontaneous burst and tonic firing activities of VP and RT neurons among the two KO and their wild-type (WT) control mice. We found that in WT mice, 50% somatosensory RT neurons and less than 1% VP neurons were nociceptive. Percentages of nociceptive neurons decreased in the RT and VP in the Cav3.2 KO mice. Cav3.1 KO lost most burst firing in VP. In Cav3.2 KO, we found fewer and weakened RT burst firing and tonic RT firing lost their regularity. Interestingly, Cav3.2 KO also showed increased and stronger VP burst firing. In the second part of the present study, the responsiveness of the VP and RT burst firing to tactile and noxious stimuli in the Cav3.1 and Cav3.2 KO were studied. We found that the innocuous stimulation induced response firing in VP and RT neurons were mostly burst firing, whereas noxious stimulation induced mostly single spikes. T-channel KO mice showed similar response pattern. Cav3.1 KO particularly showed less proportion of VP burst firing in response to light touch stimulation and RT neurons showed more prominently single spike firings in response to pinch stimulation compare to their WT control mice. In Cav3.2 KO, VP and RT neurons showed reduced bursts of mechanical innocuous stimulation evoked response. In laser heat stimulation evoked responses, Cav3.2 KO RT neurons showed reduced burst firing response in both percentage and amplitude. Furthermore, Cav3.2 KO VP and RT neurons had longer response onset latencies in 1.5 T electrical stimulation and laser heat stimulation. In the third part of this study, we analyzed thalamic neuron activities in a longer time scale to see whether T channel deficits interfered with intra thalamic interactions. A slow reciprocal VP and RT oscillations was found. This oscillation was modality independent, but it was weakened in Cav3.1 and Cav3.2 KO mice. The results showed that T-channel is important in thalamic burst rhythm, slow rhythm, and thalamocortical neuron and reticular neuron interaction. These factors may contribute to rodent pain function. In conclusion, T-channels are involved in thalamic VP and RT rhythmic activities. The changes in thalamic rhythmicity might contribute to the changed nocifensive behaviors in the T channel defective mice. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43887 |
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