A Mathematical Model of a Midbrain Dopamine Neuron Identifies Two Slow Variables Likely Responsible for Bursts Evoked by SK Channel Antagonists and Terminated by Depolarization Block.
A Mathematical Model of a Midbrain Dopamine Neuron Identifies Two Slow Variables Likely Responsible for Bursts Evoked by SK Channel Antagonists and Terminated by Depolarization Block.
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DOI：
10.1186/s13408-015-0017-6
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发表时间：
2015
影响因子：
2.3
通讯作者：
Canavier CC
中科院分区：
文献类型：
--
作者：
Yu N;Canavier CC
中脑多巴胺神经元表现出一种新型的爆发，我们称之为“倒置方波爆发”时，暴露于钙激活的小电导（SK）的K+通道阻断剂在体外。这种类型的爆发有三个阶段：超极化沉默，尖峰和去极化阻滞。我们发现，两个慢变量需要这种类型的突发，我们发现，三维分叉图倒置方波突发是一个折叠的表面上（去极化）和下（超极化）分支。L型Ca2+通道的激活在很大程度上支持了这些分支之间的分离。尖峰起始于下分支折叠边的不变圆分叉上的鞍节点，并且轨迹围绕上分支上的不稳定不动点螺旋。尖峰在超临界Hopf分叉处终止，但轨迹保持在上分支上，直到它碰到上折叠边缘上的鞍节点并下降到下分支。两个慢变量的贡献如下。钠通道失活的第二个缓慢组分主要负责尖峰的起始和终止。去极化平台期的终止主要是由于ERG K+电流的缓慢激活。本文所确定的机制和缓慢过程可能有助于在体内多巴胺神经元的不同亚群中不同程度地爆发以及进入去极化阻滞和从去极化阻滞恢复。
Midbrain dopamine neurons exhibit a novel type of bursting that we call “inverted square wave bursting” when exposed to Ca2+-activated small conductance (SK) K+ channel blockers in vitro. This type of bursting has three phases: hyperpolarized silence, spiking, and depolarization block. We find that two slow variables are required for this type of bursting, and we show that the three-dimensional bifurcation diagram for inverted square wave bursting is a folded surface with upper (depolarized) and lower (hyperpolarized) branches. The activation of the L-type Ca2+ channel largely supports the separation between these branches. Spiking is initiated at a saddle node on an invariant circle bifurcation at the folded edge of the lower branch and the trajectory spirals around the unstable fixed points on the upper branch. Spiking is terminated at a supercritical Hopf bifurcation, but the trajectory remains on the upper branch until it hits a saddle node on the upper folded edge and drops to the lower branch. The two slow variables contribute as follows. A second, slow component of sodium channel inactivation is largely responsible for the initiation and termination of spiking. The slow activation of the ether-a-go-go-related (ERG) K+ current is largely responsible for termination of the depolarized plateau. The mechanisms and slow processes identified herein may contribute to bursting as well as entry into and recovery from the depolarization block to different degrees in different subpopulations of dopamine neurons in vivo.
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影响因子：
4.3
作者：
Drion G;Massotte L;Sepulchre R;Seutin V
通讯作者：
Seutin V
影响因子：
1.9
作者：
BAER, SM;ERNEUX, T;RINZEL, J
通讯作者：
RINZEL, J
影响因子：
2.5
作者：
Canavier, C. C.;Landry, R. S.
通讯作者：
Landry, R. S.
影响因子：
5.3
作者：
Hart, Andrew S.;Rutledge, Robb B.;Phillips, Paul E. M.
通讯作者：
Phillips, Paul E. M.
影响因子：
6.1
作者：
FREEMAN, AS;MELTZER, LT;BUNNEY, BS
通讯作者：
BUNNEY, BS