Doiron B, Longtin A, Turner R W, Maler L
Physics Department, University of Ottawa, Ottawa, Ontario K1N 6N5, Canada.
J Neurophysiol. 2001 Oct;86(4):1523-45. doi: 10.1152/jn.2001.86.4.1523.
Pyramidal cells of the electrosensory lateral line lobe (ELL) of the weakly electric fish Apteronotus leptorhynchus have been shown to produce oscillatory burst discharge in the gamma-frequency range (20-80 Hz) in response to constant depolarizing stimuli. Previous in vitro studies have shown that these bursts arise through a recurring spike backpropagation from soma to apical dendrites that is conditional on the frequency of action potential discharge ("conditional backpropagation"). Spike bursts are characterized by a progressive decrease in inter-spike intervals (ISIs), and an increase of dendritic spike duration and the amplitude of a somatic depolarizing afterpotential (DAP). The bursts are terminated when a high-frequency somatic spike doublet exceeds the dendritic spike refractory period, preventing spike backpropagation. We present a detailed multi-compartmental model of an ELL basilar pyramidal cell to simulate somatic and dendritic spike discharge and test the conditions necessary to produce a burst output. The model ionic channels are described by modified Hodgkin-Huxley equations and distributed over both soma and dendrites under the constraint of available immunocytochemical and electrophysiological data. The currents modeled are somatic and dendritic sodium and potassium involved in action potential generation, somatic and proximal apical dendritic persistent sodium, and K(V)3.3 and fast transient A-like potassium channels distributed over the entire model cell. The core model produces realistic somatic and dendritic spikes, differential spike refractory periods, and a somatic DAP. However, the core model does not produce oscillatory spike bursts with constant depolarizing stimuli. We find that a cumulative inactivation of potassium channels underlying dendritic spike repolarization is a necessary condition for the model to produce a sustained gamma-frequency burst pattern matching experimental results. This cumulative inactivation accounts for a frequency-dependent broadening of dendritic spikes and results in a conditional failure of backpropagation when the intraburst ISI exceeds dendritic spike refractory period, terminating the burst. These findings implicate ion channels involved in repolarizing dendritic spikes as being central to the process of conditional backpropagation and oscillatory burst discharge in this principal sensory output neuron of the ELL.
研究表明，弱电鱼细吻无背电鳗（Apteronotus leptorhynchus）的电感觉侧线叶（ELL）中的锥体细胞，在受到持续去极化刺激时，会产生γ频率范围（20 - 80赫兹）的振荡爆发式放电。先前的体外研究表明，这些爆发是通过从胞体到顶端树突的反复尖峰反向传播产生的，这种反向传播取决于动作电位放电的频率（“条件性反向传播”）。尖峰爆发的特征是峰峰间期（ISI）逐渐减小，树突尖峰持续时间增加，以及胞体去极化后电位（DAP）的幅度增加。当高频的胞体尖峰双峰超过树突尖峰不应期，阻止尖峰反向传播时，爆发终止。我们提出了一个ELL基底锥体细胞的详细多房室模型，以模拟胞体和树突的尖峰放电，并测试产生爆发输出所需的条件。模型中的离子通道由修改后的霍奇金 - 赫胥黎方程描述，并根据可用的免疫细胞化学和电生理数据分布在胞体和树突上。所模拟的电流包括参与动作电位产生的胞体和树突钠电流与钾电流、胞体和近端顶端树突的持续性钠电流，以及分布在整个模型细胞上的K(V)3.3和快速瞬态A样钾通道。核心模型产生了逼真的胞体和树突尖峰、不同的尖峰不应期，以及胞体DAP。然而，核心模型在持续去极化刺激下不会产生振荡尖峰爆发。我们发现，树突尖峰复极化所涉及的钾通道的累积失活，是模型产生与实验结果匹配的持续γ频率爆发模式的必要条件。这种累积失活导致树突尖峰的频率依赖性展宽，并在爆发内ISI超过树突尖峰不应期时导致反向传播的条件性失败，从而终止爆发。这些发现表明，参与树突尖峰复极化的离子通道是ELL这个主要感觉输出神经元中条件性反向传播和振荡爆发放电过程的核心。
