DEVELOPMENT OF LOCAL CIRCUITS IN CEREBRAL CORTEX

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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.