DEVELOPMENT OF NETWORK ACTIVITY IN THALAMOCORTICAL CIRCUITS

丘脑皮层网络的发展在活动独立的过程中进行， 在此期间，基本轴突连接形成，随后是 活动依赖性阶段，在此期间，这些轴突连接被细化 以实现高解剖学和突触特异性特征， 成人大脑 在这一活动依赖性阶段， 据信谷氨酸正性肌力受体NMDA亚型 突触可塑性 在哺乳动物的视觉系统中， 纤维在视觉体验之前分离成眼睛特定层， 这种分离被自发活动的阻断所破坏。 这些 结果表明，非视觉驱动的活动可能发挥关键作用， 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，前脑的自发活动，如图所示， 脑电图（EEG）越来越具有以下特征： 成年动物。 EEG的这种发展包括外观和 正常（例如纺锤波）和异常（例如缺失）的成熟 癫痫发作）丘脑皮质系统的同步振荡。 最近 我们已经证明，雪貂的LGNd，作为体外切片保存， 表现出自发的同步振荡特性， 发育和成人大脑原位，这种体外制剂是 用于突触和网络发育的细胞分析 丘脑皮质系统的特性。 在本研究中，我们 将研究非视觉发育的细胞机制， 雪貂LGNd的相关同步活动， LGNd内的GABA能抑制，NMDA受体对LGNd的贡献， 丘脑皮层单突触EPSP，以及对 皮层内GABA能抑制性中间神经元的NMDA受体。 这些 研究将提供一个细胞水平的理解， 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， 振荡和突触功能将导致更好地理解 哺乳动物突触连接和功能的发展 前脑和可能的治疗选择，以预防 全身性癫痫

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.