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.
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