ACTIVITY REFINES CORTICOSPINAL TERMINATIONS

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DESCRIPTION (Investigator's Abstract): The overall objectives of the proposed research are to gain an understanding of how function of the corticospinal (CS) system at early postnatal stages affects the later development of this system and the motor behaviors that it mediates. The PI has begun to study the activity-dependence of postnatal CS development. The proposed experiments are based on the PI's recent finding that the postnatal refinement of CS terminations in cats is activity-dependent. When neural activity in sensorimotor cortex was blocked unilaterally during early postnatal development, the CS system originating from the (active) sensorimotor cortex had bilateral terminations in the spinal gray matter later in development, when age-matched controls have predominantly contralateral CS terminations. This activity-dependence was demonstrated by infusing the GABA agonist muscimol continuously into sensorimotor cortex to hyperpolarize neurons. The PI hypothesizes that blocking CS activity prevents the elimination of transient ipsilateral terminations of the cat CS system, which are normally present. He also hypothesizes that this anatomical reorganization impairs the behaviors that the CS system mediates. This proposal has two aims to test theses hypotheses. The first is to determine the activity-dependence and time course of postnatal refinement of corticospinal terminations. The PI will block activity in cat sensorimotor cortex during early postnatal development and map the connections of the CS system later in development and in maturity. In the second aim, the PI will determine the effects of continuous postnatal blockade of neural activity in sensorimotor cortex on performance of skilled forelimb movements. The PI will analyze the kinematic, dynamic, and electromyographic changes during prehension in mature cats, correlating these changes with alterations in the topography of CS terminations produced by neonatal activity blockade. Experiments will determine if inactivation of the motor cortex with bilateral CS terminations impairs reaching and grasping performance bilaterally, or only contralaterally, as in normal animals. The changes in the organization of this system that will be studied are said have important clinical significance: The CS is reorganized in patients with cerebral palsy that sustained neonatal injury to the sensorimotor cortex. These patients have incapacitating motor impairments that can, in part, be attributed to reorganization of CS terminations.