Ionic mechanisms underlying synchronized oscillations and propagating waves in a model of ferret thalamic slices
Ionic mechanisms underlying synchronized oscillations and propagating waves in a model of ferret thalamic slices
复制标题
DOI：
10.1152/jn.1996.76.3.2049
复制
发表时间：
1996-09-01
影响因子：
2.5
通讯作者：
Sejnowski, TJ
中科院分区：
文献类型：
--
作者：
Destexhe, A;Bal, T;Sejnowski, TJ
1。基于雪貂丘脑切片中的电生理测量，开发了丘脑皮质（TC）和丘脑网状（RE）神经元的网络模型。单室TC和RE细胞包括Hodgkin-Huxley类型动力学的电压和钙敏感电流。突触电流通过α-Amino-3-羟基-5-甲基-4-异沙唑丙酸（AMPA），γ-氨基丁基酸-A（GABA（a））和GABA（b）受体的动力学模型进行建模。该模型成功地重现了在体外观察到的纺锤体和慢速双瓜氨酸诱导的振荡的特征。这两种类型的振荡的特征都取决于TC和RE细胞的内在特性及其互连性模式。3。振荡是由于TC和RE细胞之间的相互募集而组织的，这是由于它们的相互连接性和爆发性能。 TC细胞在RE细胞中引起AMPA介导的兴奋性突触后电位（EPSP），而RE细胞在TC细胞中引起了GABA（A）和GABA（A）和GABA（B）抑制性突触后电位（IPSP）的混合物。由于存在T电流，因此足够强的EPSP可能会引起RE细胞的突发，并且TC细胞可能会在GABA能IPSPS后产生反弹爆发。在这些条件下，TC和RE细胞之间的相互作用产生了持续的振荡4。在任何细胞中没有自发振荡的情况下，TC-RE网络保持静止。刺激TC或RE神经元可以启动频率为9-11 Hz的主轴振荡。一些自发振荡的TC神经元将整个网络模型招募到“打蜡和蜡”振荡中。这些“引发剂”细胞可能是TC细胞的一小部分。5。在细胞内记录中，TC细胞在一系列爆发后显示出降低爆发的能力。在网络模型中，通过假设通过TC细胞中的钙结合蛋白进行活性依赖于I-H的I-H进行的“纺纱”阶段，如两个细胞模型中所示。6。在全球抑制GABA（a）抑制后，被抑制的RE细胞产生了长时间的爆发放电，从而引起了TC细胞中的强GABA（B）介导的电流。 TC细胞中慢速IPSP的增强也归因于GABA（B）介导的电流激活中的合作。这些缓慢的IPSP募集了TC，并将细胞重新升级到更慢的打蜡和振荡振荡（3-4 Hz），这些振荡更加同步。7。 TC对TC的局部轴突化轴承化，使振荡通过网络传播。随着越来越多的细胞逐渐募集，从单个焦点开始的振荡诱导了传播波前。由于在TC细胞中I-H的上调，振荡的减弱也繁殖，从而导致纺锤活性波，如实验中所观察到的。8。模型中传播波的时空特性高度取决于TC细胞的内在特性。与双瓜氨酸诱导的振荡相比，纺锤体的尖峰活性的空间模式明显不同，并取决于TC细胞的反弹爆发行为。 I-H的上调产生了一个难治时期，因此碰撞的纺锤波合并为单个振荡并熄灭。最后，减少I-H电导导致持续振荡9。丘脑网络中细胞的两个关键特性可能解释了主轴振荡的启动，传播和终止，TC细胞中I-H的活性依赖性上调以及TC和RE细胞之间的局部轴突投影。此外，该模型预测GABA（B）反应的非线性刺激依赖性是GABA受体（a）受体块后长时间同步放电的起源。
1. A network model of thalamocortical (TC) and thalamic reticular (RE) neurons was developed based on electrophysiological measurements in ferret thalamic slices. Single-compartment TC and RE cells included voltage- and calcium-sensitive currents de scribed by Hodgkin-Huxley type of kinetics. Synaptic currents were modeled by kinetic models of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), gamma-aminobutyric acid-A (GABA(A)) and GABA(B) receptors.2. The model reproduced successfully the characteristics of spindle and slow bicuculline-induced oscillations observed in vitro. The characteristics of these two types of oscillations depended on both the intrinsic properties of TC and RE cells and their pattern of interconnectivity.3. The oscillations were organized by the reciprocal recruitment between TC and RE cells, due to their mutual connectivity and bursting properties. TC cells elicited AMPA-mediated excitatory postsynaptic potentials (EPSPs) in RE cells, whereas RE cells elicited a mixture of GABA(A) and GABA(B) inhibitory postsynaptic potentials (IPSPs) in TC cells. Because of the presence of a T current, sufficiently strong EPSPs could elicit a burst in RE cells, and TC cells could generate a rebound burst following GABAergic IPSPs. Under these conditions, interaction between the TC and RE cells produced sustained oscillations.4. In the absence of spontaneous oscillation in any cell, the TC-RE network remained quiescent. Spindle oscillations with a frequency of 9-11 Hz could be initiated by stimulation of either TC or RE neurons. A few spontaneously oscillating TC neurons recruited the entire network model into a ''waxing-and-waning'' oscillation. These ''initiator'' cells could be an extremely small proportion of TC cells.5. In intracellular recordings, TC cells display a reduced ability for burst firing after a sequence of bursts. The ''waning'' phase of spindles was reproduced in the network model by assuming an activity-dependent upregulation of I-h Operating via a calcium-binding protein in TC cells, as shown previously in a two-cell model.6. Following the global suppression of GABA(A) inhibition, the disinhibited RE cells produced prolonged burst discharges that elicited strong GABA(B)-mediated currents in TC cells. The enhancement of slow IPSPs in TC cells was also due to cooperativity in the activation of GABA(B)-mediated current. These slow IPSPs recruited TC and RE cells into slower waxing-and-waning oscillations (3-4 Hz) that were even more highly synchronized.7. Local axonal arborization of the TC to RE and RE to TC projections allowed oscillations to propagate through the network. An oscillation starting at a single focus induced a propagating wavefront as more cells were recruited progressively. The waning of the oscillation also propagated due to upregulation of I-h in TC cells, leading to waves of spindle activity as observed in experiments.8. The spatiotemporal properties of propagating waves in the model were highly dependent on the intrinsic properties of TC cells. The spatial pattern of spiking activity was markedly different for spindles compared with bicuculline-induced oscillations and depended on the rebound burst behavior of TC cells. The upregulation of I-h produced a refractory period so that colliding spindle waves merged into a single oscillation and extinguished. Finally, reducing the I-h conductance led to sustained oscillations.9. Two key properties of cells in the thalamic network may account for the initiation, propagation, and termination of spindle oscillations, the activity-dependent upregulation of I-h in TC cells, and the localized axonal projections between TC and RE cells. In addition, the model predicts that a nonlinear stimulus dependency of GABA(B) responses accounts for the genesis of prolonged synchronized discharges following block of GABA(A) receptors.