- 學位論文
在一個純間隙連接的神經迴路中以連續兩次神經衝動誘導出高頻震盪
Induction of High-frequency Oscillations in a Junction-coupled Network by a paired spike
摘要
在脊椎動物腦部的許多區域以及非脊椎動物的中樞神經系統中,於一群神經細胞中誘導出頻率最高可達每秒600次的神經衝動(spike)震盪在過去曾被觀測到。根據過去的許多研究指出，電突觸(electrical synapse)對這種高頻的神經衝動震盪扮演著相當重要的角色。透過電腦模擬與電生理實驗，雖然很多研究認為在化學突觸的參與下，神經震盪可以很容易被誘導出來。然而，非常多的研究指出，這種高頻震盪與化學突觸無關。只和電突觸以及神經本身具有的離子通道相關。雖然有許多可能機制利用電腦模擬陸續地被提出，但是這些機制都未能找到合適的神經系統來給予驗證。更不用說高頻震盪是如何開始形成的。在本研究中，藉由電腦模擬，我們得到如下的結果：透過兩次密集的神經衝動，在一個以純電突觸相連結的封閉神經迴路中，高頻震盪可以很容易地被誘導出來。更進一步的，我們在螯蝦中，一個以純電突觸相連結的側邊巨大神經(lateral giant neuron)所構成封閉神經迴路上，採用同樣的方式也可以誘導出高達每秒626次的高頻神經衝動震盪。 詳細分析發現，這種方式所產生的高頻震盪取決於弱間隙連接以及神經衝動後恢復期間(refractory period)所新產生動作電位(action potential)的傳遞行為有關。因為這個新產生的動作電位很難被激發出來。即使產生了，在神經軸索(axon)的傳遞也會變慢，並且難以通過細胞間的間隙連接。結果，當兩個密集的神經衝動發生在一個間隙連接附近，只有第一個衝動會通過此間隙連接。而此兩衝動會隨著在神經軸索上行進的距離變長而逐漸拉開，於是當它們在碰到下一個間隙連接時，會因為它們之間的時間間隔拉大了而都能成功通過此電突觸。此一現象發生在一個封閉的神經迴路中時，由於一個方向有兩個衝動在傳遞，另一個方向則只有一個衝動在跑。當這些衝動撞在一起時，兩方向的第一個衝動會互撞消逝而只剩下一個衝動在此封閉迴路不停的繞下去。此時，這一封閉的神經迴路就成為一個震盪中心持續產生動作電位。由於這種高頻震盪是由一個脈衝在封閉的神經迴圈中持續的運行，震盪頻率便可以由一個脈衝繞此迴圈一週所需的時間來決定。 最後，透過電腦模擬及電生理實驗，我們也發現如果能在震盪的衝動之間，人為的產生另一個動作電位，便可以終止此震盪。這方法或許對癲癇症的處置可以些提供有價值引導。
並列摘要
High-frequency oscillation (HFO) up to 600 Hz in grouped neurons have been observed in the brain areas of vertebrates and central nerve system of invertebrates. Many studies indicate electrical synapses play key roles. With the participation of chemical synapses, neuronal oscillation can be easily generated either by computer simulation or real electrophysiological measurement. However, many reports indicate that HFO is independent of chemical synapse, but depend on gap junction and intrinsic properties of ion channels of participating neurons. Although several mechanisms have been suggested from computer simulations, no one has been verified in real neurons. It is even difficult to understand how HFO is initiated. Here we demonstrate how a paired-spike induces HFO in a gap-junction-coupled network which formed a closed loop and contained only three cells. Furthermore, HFO up to 626 Hz in an electrically coupled network of crayfish was also displayed without the involvement of chemical synapses. In fact, the oscillation only depends on weakly-coupled gap junctions and associated behaviors of spike propagation during refractory period of preceding action potential. For initiating oscillations, it is absolutely essential that the second spike is elicited during the refractory period. Even a spike is elicited; it suffers from slow propagation speed and a tendency for failure through low conductance junctions. Thus, paired-spikes with a short spike interval induce only one trans-junctional spike. At distant synaptic sites, two trans-junctional spikes are triggered because the spike interval increases with spike propagation. Consequently, trans-junctional spikes collide in a gap-junction-coupled network. The remaining single spike reverberates in a loop that serves as an oscillation centre. Since HFO is generated by spike reverberation in a closed loop. The oscillating frequency is decided by the spike traveling time through the closed loop of oscillating center. Further analysis by both simulation and electrophysiological experiment indicated that a simple insertion of spike into the oscillating spikes was verified being able to terminate the paired-spike-elicited HFO. This simple method might provide a valuable hint for the treatment of epilepsy.