A MODEL OF THE ELECTROPHYSIOLOGICAL PROPERTIES OF THALAMOCORTICAL RELAY NEURONS
A MODEL OF THE ELECTROPHYSIOLOGICAL PROPERTIES OF THALAMOCORTICAL RELAY NEURONS
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DOI：
10.1152/jn.1992.68.4.1384
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发表时间：
1992-10-01
影响因子：
2.5
通讯作者：
HUGUENARD, JR
中科院分区：
文献类型：
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作者：
MCCORMICK, DA;HUGUENARD, JR
1. 部分基于电压依赖性和通过电压-平静技术详细描述的离子电流动力学，构建了啮齿动物和猫背外侧膝状核中单个丘脑皮质中继神经元的电生理特性模型。该模型简化了单个均匀隔室的假设，并结合了快速瞬态 Na+ 电流 I(Na)；持续的、去极化激活的 Na+ 电流，I(Nap)；低阈值 Ca2+ 电流，I(T)；高阈值 Ca2+ 电流，I(L)； Ca2+ 激活的 K+ 电流，I(C)；瞬态和去极化激活的 K+ 电流，I(A)；缓慢失活和去极化激活的 K+ 电流，I(K2)；超极化激活的阳离子电流，I(h)； K+和Na+漏电流I(Kleak)和I(Naleak)。2．通过单独检查每种电流对被动膜反应的影响，初步研究了各种离子电流对丘脑皮质中继神经元电生理特性的影响。两个漏电流 I(Kleak) 和 I(Naleak) 在很大程度上决定了模型神经元的静息膜电位和表观输入电阻。添加 I(A) 会导致模型细胞对去极化电流脉冲的响应延迟，而添加 I(K2) 或 I(L) 与 I(C) 组合会导致对去极化的响应显着且长期降低。添加 I(h) 导致响应超极化的消光“下垂”，而添加 I(T) 则导致超极化后 Ca2+ 峰值大幅反弹。最后，I(Nap)的加入导致去极化增强。3．使用活动电流 I(T)、I(L)、I(A)、I(C) 和 I(K2) 成功模拟了啮齿动物神经元的低阈值 Ca2+ 尖峰。低阈值 Ca2+ 电流 I(T) 产生低阈值 Ca2+ 尖峰。瞬态 K+ 电流 I(A) 减慢了上升速率并降低了低阈值 Ca2+ 尖峰的峰值幅度，而缓慢失活的 K+ 电流 I(K2) 极大地促进了 Ca2+ 尖峰的复极化。在 Ca2+ 尖峰峰值期间 I(L) 的激活导致 I(C) 的激活，这也有助于 Ca2+ 尖峰的复极化。任何一个 K+ 电流的减少都会导致另外两个 K+ 电流的增加，从而导致 Ca2+ 峰值的变化比单独根据每个离子电流的幅度所预期的变化要小得多。4．各种 K+ 电流 I(A)、I(K2) 和 I(C) 的激活也导致模型神经元的明显整流，使得对去极化电流脉冲的响应远小于对超极化电流脉冲的响应。5。快速、依赖 Na+ 的动作电位主要由 I(C) 在膜电位正至 -60 mV 时复极化，I(A) 和 I(K2) 的贡献较小。相反，I(A)和I(K2)形成动作电位之间流动的离子电流的主要成分，因此减慢了动作电位产生的速率。6．添加超极化激活的阳离子电流 I(h) 导致超极化时的去极化下垂，并在低阈值 Ca2+ 尖峰后产生明显的后超极化。在低阈值 Ca2+ 尖峰产生期间，I(h) 失活，导致膜电位在 Ca2+ 尖峰复极化时降至更负的水平。随后激活I(h)导致膜电位复极化，因此出现后超极化。7．节律性低阈值 Ca2+ 尖峰和爆发生成已成功建模，并且关键取决于 I(T)、I(h) 以及泄漏电流 I(Kleak) 和 I(Naleak)。有节奏的 Ca2+ 峰值产生的频率和幅度受到 I(h)、I(T) 和 I(Kleak) 幅度的强烈调节。增加 g(h) 的最大电导导致节奏爆发的产生从 0.5 Hz 增加到最大 4 Hz。将I(h) 的电压依赖性改变+/- 10 mV 会导致胸腺Ca2+ 尖峰产生频率分别增加和减少，并分别导致细胞维持节律振荡的能力减少和增加。8．节律振荡期间模型对去极化输入的响应与强直去极化期间明显不同。在节律振荡期间，模型细胞的去极化导致瞬态爆发响应和节律爆发放电的破坏，而在强直放电模式中应用相同的去极化电流脉冲导致一系列动作电位，没有表现出尖峰频率适应。9。总之，目前的丘脑皮质中继细胞模型表明，这些神经元中的各种 K+ 电流不仅有助于 Na+ 的复极化，还有助于低阈值 Ca2+ 尖峰的复极化，控制重复放电的时间特征，并在静息膜电位下产生神经元的明显整流。离子电流 I(T) 和 I(h) 与节律性低阈值 Ca2+ 尖峰生成密切相关，这也很大程度上取决于决定细胞膜电位和表观输入电阻的各种“泄漏”电导的状态。这些发现证实并扩展了先前基于体内和体外获得的丘脑皮质细胞的细胞内记录的建议。
1. A model of the electrophysiological properties of single thalamocortical relay neurons in the rodent and cat dorsal lateral geniculate nucleus was constructed, based in part on teh voltae dependence and kinetics of ionic currents detailed with voltage-calmp techniques. The model made the simplifying assumption of a single uniform compartment an incorported a fast and transient Na+ current, I(Na); a presistent, depolarization-activated Na+ current, I(Nap); a low-threshold Ca2+ current, I(T); a high-threshold Ca2+ current, I(L); a Ca2+-activated K+ current, I(C); a transient and depolarization-activated K+ current, I(A); a slowly inactivating and depolarization-activated K+ current, I(K2); a hyperpolarization-activated cation current, I(h); and K+ and Na+ leak currents I(Kleak) and I(Naleak).2. The effects of the various ionic current on the electrophyisological properties of thalamocortical relay neurons were initially investigated through examining the effect of each current individually on passive membrane responses. The two leak currents, I(Kleak) and I(Naleak), determined in large part the resting membrane potential and the apparent input resistance of the model neuron. Addition of I(A) resulted in a delaty in the response of the model cell to a depolarizing current pulse, whereas addition of I(K2), or I(L) combined with I(C), resulted in a marked and prolonged decrease in the respnse to depolarization. Addition of I(h) resulted in a deplarizing "sag" in respnse to hyperpolarization, hwereas addition of I(T) resulted in a large rebound Ca2+ spike after hyperpolarization. Finally, addition of I(Nap) resulted in enhancement of depolarization.3. The low-threshold Ca2+ spike of rodent neurons was successfully modeled with the active currents I(T), I(L), I(A), I(C) and I(K2). The low-threshold Ca2+ current I(T) generated the low-threshold Ca2+ spike. The transient K+ current I(A) slowed the rate of rise and reduced the peak amplitude of the low-threshold Ca2+ spike, whereas the slowly inactivating K+ current I(K2) contributed greatly to the repolarization of the Ca2+ spike. Activation of I(L) during the peak of the Ca2+ spike led to activation of I(C), which also contributed to the repolarization of the Ca2+ spike. Reduction of any one of the K+ currents resulted in an increase n the other two, therby resulting in substantially smaller changes in the Ca2+ spike than would be expected on the basis of the amplitude of each ionic current alone.4. Activation of the various K+ currents, I(A), I(K2), and I(C), also resulted in apparent rectification of the model neuron such that the response to a depolarizing current pulse was substantially smaller than the response to a hyperpolarizing current pulse.5. Fast, Na+-dependent actionpotentials were repolarized largely by I(C) at membrane potentials positive to -60 mV, with smaller contributions by I(A) and I(K2). In contrast, I(A) and I(K2) formed a major component of the ionic currents flowing in between action potentials and therfore slowed the rate of action potential generation.6. Addition of the hyperpolarization activated cation current I(h) resulted in adepolarizing sag on hyperpolarization and generated an apparent afterhyperpolarization after a low-threshold Ca2+ spike. During the generation of a low-threshold Ca2+ spike, I(h) deactivated, resulting in the membrane potential's fallin to a more negative level on repolarization of the Ca2+ spike. Subsequent activation of I(h) resulted in repolarization of the membrane potential and therefore the appearance of an afterhyperpolarization.7. Rhythmic low-threshold Ca2+ spikes and burst generation were successfully modeled and depended critically on I(T), I(h), and the leak currents I(Kleak) and I(Naleak). The frequency and amplitude of rhythmic Ca2+ spike generation was strongly modulated by the amplitude of I(h), I(T), and I(Kleak). Increasing the maximal conductance of g(h) resulted in an increase in rhythmic burst generation from 0.5 to a maximum of 4 Hz. Shifting the voltage dependence of I(h) by +/- 10 mV resulted in an increase and decrease, respectively, of the frequency of thythmic Ca2+ spike generation and a decrease and increase, respectively, of the ability of the cell to maintain rhythmic oscillation.8. The response of the model to depolarizing inputs was markedly different during rhythmic oscillation thatn during tonic depolarization. During rhythmic oscillation, depolarization of the model cell resulted in a transient burst response and disruption of rhythmic burst discharges, whereas application of the same depolarizing current pulse in the tonic firing mode resulted in a train of action potentials that displayed no spike frequency adaptation.9. In summary, the present model of thalamocortical relay cells suggests that the various K+ currents in these neurons contribute to the repolarization of not only Na+ but also low-threshold Ca2+ spikes, control the temporal characteristics of repetitive firing, and generate an apparent rectification of the neuron at resting membrane potentials. The ionic corrents I(T) and I(h) are critically involeve in rhythmic low-threshold Ca2+ spike generation, which also depends critically on the status of the various "leak" conductance that determine the membrane potential and apparent input resistance of the cell. These finding confirm and extend previuos suggestions based on intracellular recordings of thalamocortical realy cells obtained in vivo and in vitro.