DEVELOPMENT OF LOCAL CIRCUITS IN CEREBRAL CORTEX

这项研究计划的目的是 破译运动功能恢复的机制 继先天或后天神经疾病之后。尽管有几个 大脑结构参与了这个恢复过程，其中一个 重要的结构是运动皮质。在运动皮质内 是身体主要部位的体位表现，其中每一个 包含不同移动的多个非连续表示形式 模式。可以在使用中修改运动表示区- 依赖的方式，在感觉-运动扰动之后和在 获得运动技能。运动表现图的柔韧性 在出生后发育阶段尤其戏剧性，而且是 被认为与获得新的运动技能有关。 现有数据表明，运动皮质内的内在联系 链接该分布式网络内的神经元以执行协调的、 多关节动作。很可能类似的突触相互作用 也参与运动皮质的依赖使用的可塑性。这个 拟议中的研究将检验这一假设，即 运动皮质的功能组织依赖于 运动皮质内的内在突触通路。 这一假说预言，运动表征的发展 与皮质内模式的相应变化有关 关系。为了检验这一预测，我们将检验常态 运动皮质内部回路的发育模式。这个 大鼠的运动表征的发展将被揭示 微刺激技术。神经解剖束追踪技术将 用来确定内源性突触的发育和细化 这些代表区之间的路径。此外，还包括 属于几类皮质神经元的内源性轴突将 使用神经解剖学和电生理学程序进行检查。 将特别侧重于研究 属于锥体束神经元的内源性轴突侧支 将运动皮质的输出提供给脊髓运动神经元池。 我们的工作假说还预测了运动的异常发展 由感觉-运动操作引起的表征与 大脑皮质内回路的异常发育。为了验证这一预测，我们 将考察实验操作对发育的影响 这些本征电路。在这些研究中，剪裁的效果 肌间触觉(胡须)对运动发育的影响 将检查表示区和内在联系的范围。这个 上述电生理和解剖学方法也将 用于这些实验。这一方法将作为一种模式 研究在不同的情况下摘除效应器官的效果 发展阶段，关于政府职能组织的发展 大脑皮层。这些数据对于阐明 神经系统代偿的神经生物学机制 扰乱和恢复行为功能，因此 与了解先天性运动的神经病理学有关 像脑瘫这样的障碍。

The aim of the research program, of which this application is a part, is to decipher the mechanisms by which restitution of motor function occurs following congenital or acquired neurological disorders. Although several brain structures are involved in this recovery process, one of the important structures is the motor cortex. Within the motor cortex there are somatotopic representations of the major body parts, and each of these contains multiple, non contiguous representations of different movement patterns. Movement representation zones can be modified in a use- dependent fashion, following sensory-motor perturbations and during the acquisition of motor skills. The pliability of motor representation maps is particularly dramatic during the postnatal developmental period, and is thought to be correlated with the acquisition of novel motor skills. Available data indicate that intrinsic connections within the motor cortex link neurons within this distributed network to perform coordinated, multi-jointed movements. It is likely that similar synaptic interactions are involved also in the use-dependent plasticity of the motor cortex. The proposed studies will test the hypothesis that plasticity in the functional organization of the motor cortex is dependent on changes in intrinsic synaptic pathways within the motor cortex. This hypothesis predicts that the development of movement representations is associated with corresponding changes in the patterns of intracortical connections. To test this prediction we will examine the normal developmental patterns of intrinsic circuits in the motor cortex. The development of movement representations in the rat will be revealed using microstimulation techniques. Neuroanatomical tract tracing techniques will be used to determine the development and refinement of intrinsic synaptic pathways among these representation zones. In addition, the development of intrinsic axons belonging to several classes of cortico-fugal neurons will be examined, using neuroanatomical and electrophysiological procedures. Particular emphasis will be placed on studying the development of intrinsic axon collaterals belonging to pyramidal tract neurons (PTNs) that provide output from the motor cortex to spinal motoneuron pools. Our working hypothesis also predicts that abnormal development of movement representations-induced by sensory-motor manipulations-is associated with abnormal development of intracortical circuits. To test this prediction we will examine the effects of experimental manipulations on the development of these intrinsic circuits. In these studies, the effects of clipping the mystacial vibrissae (whiskers) on the development of movement representation zones and of intrinsic connections will be examined. The electrophysiological and anatomical approaches described above will also be used for these experiments. This approach will serve as a model to study the effects of removal of an effector organ, at various developmental stages, on the development of the functional organization of the cerebral cortex. These data are necessary for the elucidation of the neurobiological mechanisms responsible for compensation from neurological disturbances and for restitution of behavioral functions, and are thus relevant for understanding the neuropathology of congenital motor disturbances such as cerebral palsy.