DEVELOPMENT OF NETWORK ACTIVITY IN THALAMOCORTICAL CIRCUITS

丘脑皮质回路网络活动的发展

• 批准号: 6112243
• 负责人: David McCormick
• 金额: $ 18.47万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112243
• 关键词: GABA receptor; NMDA receptors; action potentials; afferent nerve; brain electrical activity; cerebral cortex; developmental neurobiology; electrostimulus; ferrets; gamma aminobutyrate; glutamates; innervation; lateral geniculate body; mature animal; membrane potentials; microelectrodes; neural plasticity; neuroanatomy; newborn animals; receptor sensitivity; synapses; thalamocortical tract; thalamus; visual cortex; voltage /patch clamp

Development of thalamocortical networks proceeds in an activity-independent phase during which the basic axonal connections are formed, followed by an activity-dependent phase during which these axonal connections are refined to achieve the high anatomical and synaptic specificity characteristic of the adult brain. During this activity-dependent phase, athe activation of the NMDA subtype of glutamate inotropic receptor is believed to facilitate synaptic plasticity. In the mammalian visual system, retinogeniculate fibers segregate into eye specific layers prior to visual experience, and this segregation is disrupted by block of spontaneous activity. These results indicate that non-visually driven activity may play a key role in the determination of appropriate anatomical connections in the visual system. In addition, during this period of formation and definition of synaptic circuits, spontaneous activity in the forebrain, as represented by the electroencephalogram (EEG), is becoming more and more characteristic of the adult animal. This development of the EEG includes the appearance and maturation of both normal (e.g. spindle waves) and abnormal (e.g. absence seizures) synchronized oscillations in thalamocortical systems. Recently we have demonstrated that the ferret LGNd, maintained as a slice in vitro, exhibits spontaneous synchronized oscillations characteristic of the developing and adult brain in situ and that this in vitro preparation is useful for the cellular analysis of development of synaptic and network properties in thalamocortical systems. Therefore, in the present study, we will investigate the cellular mechanisms of development of non-visually related synchronized activity int he ferret LGNd, the development of GABAergic inhibition within the LGNd, the contribution of NMDA receptors to thalamocortical monosynaptic EPSPs, and the regulation of activation of NMDA receptors by intracortical GABAergic inhibitory interneurons. These studies will provide for a cellular level understanding for the development, generation, and propagation of synchronized network activity in thalamocortical systems. This increased understanding of synchronized oscillations and synaptic function will lead to a better understanding of the development of synaptic connections and function in the mammalian forebrain and possible to therapeutic options for the prevention of generalized seizures.

丘脑皮质网络的发展是无与伦比的 阶段形成基本的轴突连接，然后是 活动依赖性阶段，在此期间这些轴突连接得到完善 为了实现高解剖和突触特异性特征 成人大脑。 在这个活动依赖性阶段，激活 据信谷氨酸肌酸肌力受体的NMDA亚型有助于促进 突触可塑性。 在哺乳动物视觉系统中，视网膜生成 纤维在视觉体验之前将纤维隔离为特定的层，并且 这种隔离受到自发活动的障碍。 这些 结果表明，非视觉驱动的活动可能在 确定视觉中适当的解剖连接 系统。 此外，在此期间的形成和定义期间 突触电路，前脑中的自发活动，如 脑电图（EEG）正在变得越来越多 成年动物。 脑电图的这种发展包括外观和 正常（例如纺锤波）和异常（例如不存在）的成熟 癫痫发作）在丘脑皮质系统中同步振荡。 最近 我们已经证明，雪貂LGND在体外保持为切片， 展示自发同步振荡特征的特征 原位发展和成人大脑，这种体外制备是 可用于突触和网络发展的细胞分析 丘脑皮质系统中的特性。 因此，在本研究中，我们 将研究非视觉发展的细胞机制 相关同步活动在ferret lgnd，发展 LGND内的GABA能抑制作用，NMDA受体对 丘脑皮质单突触EPSP，并调节激活 心脏内GABA能抑制性神经元的NMDA受体。 这些 研究将为细胞水平理解 同步网络活动的开发，生成和传播 在丘脑皮质系统中。 对同步的这种增加的理解 振荡和突触功能将使人们更好地理解 哺乳动物中突触连接和功能的发展 前脑，并可能采取预防治疗选择 广义癫痫发作。