DEVELOPMENT OF NETWORK ACTIVITY IN THALAMOCORTICAL CIRCUITS

丘脑皮质网络的发展与活动无关 形成基本轴突连接的阶段，之后是 活动依赖阶段，在此期间这些轴突连接被细化 为了实现高度的解剖学和突触特异性特征 成人的大脑。在这一依赖活动的阶段，激活了 谷氨酸变力受体的NMDA亚型被认为有助于 突触可塑性。在哺乳动物的视觉系统中，视黄素生成 纤维在视觉体验之前被分离成眼睛特定的层，并且 这种隔离被自发活动的阻断所打破。这些 结果表明，非视觉驱动的活动可能在 在视觉上确定适当的解剖连接 系统。此外，在这一时期的形成和定义 突触回路，前脑中的自发活动，如 脑电(EEG)，正变得越来越具有特征性 成年动物。脑电的这种发展包括出现和发展 正常(例如纺锤波)和异常(例如缺失)的成熟 癫痫)丘脑皮质系统的同步振荡。最近 我们已经证明了雪貂LGND，在体外保持为切片， 展示了自发性同步振荡的特征 在原位发育和成人脑，这种体外制剂 适用于突触和网络发育的细胞分析 丘脑皮质系统的特性。因此，在本研究中，我们 将研究非视觉发育的细胞机制 雪貂LGND之间的相关同步活动，发展 LGND内GABA能抑制，NMDA受体对 丘脑皮质单突触EPSP及其激活的调节 皮质内GABA能抑制中间神经元的NMDA受体。这些 研究将提供对细胞水平的了解 同步网络活动的开发、生成和传播 在丘脑皮质系统中。这增加了对同步的理解 振荡和突触功能将使我们更好地理解 哺乳动物突触连接和功能的发育 前脑和可能的治疗选择，以预防 全身癫痫发作。

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.