DEVELOPMENT OF THALAMOCORTICAL CONNECTIONS IN MOUSE SOMATOSENSORY CORTEX

丘脑皮层突触是感觉处理的关键环节， 新皮层及其早期发育阶段特别容易受到 异常的感官输入 它还可能在以下方面发挥重要作用： 癫痫发作的传播。 因此，了解它的发展， 对于理解正常和异常的皮质功能至关重要。 然而，令人惊讶的是，人们对它在这些地方的特性知之甚少。 早期阶段 开发一种新型的切片制剂， 功能性丘脑皮层连接，以及最近的 将全细胞记录技术应用于厚切片， 使得在细胞内研究这种突触的发育成为可能 水平 我们对急性丘脑皮层切片的初步研究 揭示了功能性丘脑皮层接触首先建立在 皮层深层（V/VI）和NMDA和非NMDA型 受体介导新形成的丘脑皮质连接。 的 皮质内抑制性连接的建立相对延迟 丘脑皮层兴奋性连接的形成 本研究 我们建议进一步研究形态和生理 新生小鼠皮层丘脑皮质突触的发育 急性切片 基于电生理学和药理学标准， 响应将被分类为NMDA或非NMDA型EPSC或 GABA能IPSC。 每种应对措施的制定将 单独检查。 将检查的属性包括空间 分布在不同的层和不同的形态类别 在出生后的头两周， 标示 将在急性切片中使用DiI进行丘脑传入神经群的检测， 与生理实验相结合，以便将 纤维的形态分布与功能部位 连接. 我们还确定了 从出生后早期动物（P0/P2）制备的丘脑皮质切片 存活并保持从丘脑投射到 在无血清的化学成分确定的培养基中培养皮质至少1-2周。 在这些培养物中，我们将检查丘脑传入神经的生长， 在培养的前两周内的树枝状模式。 将进行电生理记录，以评估哪些丘脑 投射到皮层的纤维形成功能性连接。 操纵 的生长条件，然后将进行，以确定 生理或生化因素参与的过程中， 突触发生 这些研究的结果对急性和培养的 丘脑皮层切片将有助于我们理解 正常和异常皮质功能的发展。

The thalamocortical synapse is a crucial link in sensory processing by the neocortex, and its early stages of development are particularly susceptible to abnormal sensory inputs. It may also play an important role in the propagation of epileptic seizures. Thus understanding its development is essential for understanding both normal and abnormal cortical function. Nevertheless surprisingly little is known about its properties at these early stages. The development of a novel slice preparation that retains functional thalamocortical connectivity, together with the recent application of the whole-cell recording technique to the thick slice, now make it feasible to study development of this synapse at the intracellular level. Our preliminary studies in acute thalamocortical slices have revealed that functional thalamocortical contacts are first established in the deep layers (V/VI) of the cortex and that both NMDA and nonNMDA-type receptors mediate the newly formed thalamocortical connections. The establishment of intracortical inhibitory connections is delayed relative to the formation of thalamocortical excitatory connections. In this study we propose to further examine both the morphological and physiological development of the thalamocortical synapse in neonatal mouse cortex in the acute slice. Based on electrophysiological and pharmacological criteria, responses will be classified as NMDA or non-NMDA type EPSC's or as GABAergic IPSC's. The development of each type of response will be examined separately. Properties that will be examined include the spatial distribution across different layers and on different morphological classes of neurons during the first two weeks postnatal. Labelling of the population of thalamic afferents with DiI in acute slices will be done in conjunction with the physiological experiments in order to correlate the morphological distribution of fibers with the location of functional connections. We have also determined conditions under which thalamocortical slices prepared from early postnatal animals (P0/P2) survive and maintain intact fibers projecting from the thalamus to the cortex for at least 1-2 weeks in a serum-free chemically-defined medium. In these cultures we will examine the growth of thalamic afferents and patterns of arborization in the first two weeks in culture. Electrophysiological recordings will be performed to assess which thalamic fibers projecting to the cortex form functional connections. Manipulation of the growth conditions will then be done in order to identify physiological or biochemical factors involved in the process of synaptogenesis. The results of these studies on acute and cultured thalamocortical slices will contribute to our understanding of the development of both normal and abnormal cortical function.