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雪貂丘脑切片模型中同步振荡和传播波背后的离子机制。

Ionic mechanisms underlying synchronized oscillations and propagating waves in a model of ferret thalamic slices.

作者信息

Destexhe A, Bal T, McCormick D A, Sejnowski T J

机构信息

Department of Physiology, Laval University School of Medicine, Quebec, Canada.

出版信息

J Neurophysiol. 1996 Sep;76(3):2049-70. doi: 10.1152/jn.1996.76.3.2049.

Abstract
  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 described 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 (GABAA) and GABAB 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 manual connectivity and bursting properties. TC cells elicited AMPA-mediated excitatory postsynaptic potentials (EPSPs) in RE cells, whereas RE cells elicited a mixture of GABAA and GABAB 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 Ih operating via a calcium-binding protein in TC cells, as shown previously in a two-cell model. 6. Following the global suppression of GABAA inhibition, the disinhibited RE cells produced prolonged burst discharges that elicited strong GABAB-mediated currents in TC cells. The enhancement of slow IPSPs in TC cells was also due to cooperativity in the activation of GABAB-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 Ih 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 Ih produced a refractory period so that colliding spindle waves merged into a single oscillation and extinguished. Finally, reducing the Ih 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 Ih in TC cells, and the localized axonal projections between TC and RE cells. In addition, the model predicts that a nonlinear stimulus dependency of GABAB responses accounts for the genesis of prolonged synchronized discharges following block of GABAA receptors.
摘要
  1. 基于雪貂丘脑切片的电生理测量结果,构建了丘脑皮质(TC)和丘脑网状(RE)神经元的网络模型。单室TC和RE细胞包含由霍奇金 - 赫胥黎动力学类型描述的电压和钙敏感电流。突触电流由α - 氨基 - 3 - 羟基 - 5 - 甲基 - 4 - 异恶唑丙酸(AMPA)、γ - 氨基丁酸 - A(GABAA)和GABAB受体的动力学模型进行模拟。2. 该模型成功再现了体外观察到的纺锤波和荷包牡丹碱诱导的慢振荡的特征。这两种振荡类型的特征取决于TC和RE细胞的内在特性及其相互连接模式。3. 由于TC和RE细胞的相互连接和爆发特性,振荡通过它们之间的相互募集而组织起来。TC细胞在RE细胞中引发AMPA介导的兴奋性突触后电位(EPSP),而RE细胞在TC细胞中引发GABAA和GABAB抑制性突触后电位(IPSP)的混合。由于存在T电流,足够强的EPSP可在RE细胞中引发爆发,并且TC细胞可在GABA能IPSP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持续振荡。4. 在任何细胞都不存在自发振荡的情况下,TC - RE网络保持静止。通过刺激TC或RE神经元可引发频率为9 - 11 Hz的纺锤波振荡。少数自发振荡的TC神经元可将整个网络模型募集到“增强 - 减弱”振荡中。这些“起始”细胞可能仅占TC细胞的极小比例。5. 在细胞内记录中,TC细胞在一系列爆发后爆发放电能力降低。如先前在双细胞模型中所示,通过假设TC细胞中通过钙结合蛋白对Ih进行活动依赖性上调,在网络模型中再现了纺锤波的“减弱”阶段。6. 在全局抑制GABAA抑制后,去抑制的RE细胞产生延长的爆发放电,在TC细胞中引发强烈的GABAB介导电流。TC细胞中慢IPSP的增强也归因于GABAB介导电流激活的协同作用。这些慢IPSP将TC和RE细胞募集到更慢的“增强 - 减弱”振荡(3 - 4 Hz)中,且同步性更高。7. TC到RE和RE到TC投射的局部轴突分支允许振荡在网络中传播。从单个焦点开始的振荡随着更多细胞逐渐被募集而诱导出传播的波前。振荡的减弱也由于TC细胞中Ih的上调而传播,导致实验中观察到的纺锤波活动波。8. 模型中传播波的时空特性高度依赖于TC细胞的内在特性。与荷包牡丹碱诱导的振荡相比,纺锤波的尖峰活动空间模式明显不同,并且取决于TC细胞的反弹爆发行为。Ih的上调产生了不应期,使得碰撞的纺锤波合并为单个振荡并消失。最后,降低Ih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纺锤波振荡的起始、传播和终止、TC细胞中Ih的活动依赖性上调以及TC和RE细胞之间的局部轴突投射。此外,该模型预测GABAB反应的非线性刺激依赖性解释了GABAA受体阻断后延长的同步放电的产生。

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