DEVELOPMENT OF LOCAL CIRCUITS IN CEREBRAL CORTEX

该应用程序是研究计划的一部分，其目的是 来破译运动功能恢复的机制 先天性或后天性神经系统疾病。尽管几 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层。在运动皮层内 是主要身体部位的躯体位置表征， 包含不同运动的多个非连续表示 模式. 移动表示区域可以在使用中修改- 依赖的方式，以下感觉运动扰动和期间 获得运动技能。运动表征图的柔韧性 在出生后的发育期尤为显著， 被认为与获得新的运动技能有关。 现有数据表明，运动皮层内的内在联系 将这个分布式网络中的神经元链接起来， 多关节运动。类似的突触相互作用 也参与了运动皮层的使用依赖性可塑性。的 拟议中的研究将测试这一假设，即可塑性在 运动皮层的功能组织依赖于 运动皮层内的内在突触通路。 这一假说预测，运动表征的发展 与皮质内神经元的模式的相应变化有关。 连接.为了验证这个预测，我们将检查正常的 运动皮层内在回路的发展模式。的 大鼠运动表征的发展将通过使用 微刺激技术神经解剖束追踪技术将 可用于确定内在突触的发育和完善， 这些代表区之间的通道。此外，发展 属于几类离皮质神经元的内在轴突将 使用神经解剖学和电生理学程序进行检查。 将特别着重研究 属于锥体束神经元（PTNs）的内在轴突侧支 提供从运动皮层到脊髓运动神经元池的输出。 我们的工作假设还预测， 由感觉运动操纵引起的表征与 皮质内回路的异常发育。为了验证这一预测， 将研究实验操作对发展的影响， 这些内在的电路。 在这些研究中， 对运动发展的影响 代表区和内在联系将被检查。的 上述电生理和解剖方法也将 用于这些实验。这种方法将作为一种模式， 研究效应器官切除的影响， 发展阶段，关于发展的职能组织， 大脑皮层这些数据对于阐明 神经生物学机制负责补偿神经系统 干扰和恢复行为功能，因此， 与了解先天性运动神经病理学有关 脑性瘫痪等疾病。

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.