Previous work has demonstrated survival of peptidergic, diaphorase, and pyramidal neurons in fetal cortex transplants which connect to host cortex and subcortical structures. This proposal addresses the question of whether these transplants are functional, and if so, whether this is due to appropriate connections or to trophic interactions between host and transplant. To answer whether transplants are functional, rats are first trained to perform a forelimb motor task. One week after lesioning forelimb motor cortex, one group receives fetal frontal cortex, one receives fetal cerebellar, and one receives gelfoam implants. The motor behavior of each transplanted group is compared to the gelfoam implanted controls. Following this, transplants are removed. It is hypothesized that forelimb motor function will deteriorate following removal of functional transplants. Secondly, it will be determined whether adult host brain thalamic connections to fetal parietal cortex transplants are functional. The whisker sensory barrelfield of adult rats is removed, and fetal parietal cortex transplanted into the cavity. Later, the vibrissae contralateral to the transplants are stimulated. 2-deoxyglucose is injected and the resting and stimulated transplant glucose metabolic rates determined using a double label autoradiographic method. Transplants with functional host connections should be metabolically activated during the whisker sensory stimulation. Lastly, trophic effects of fetal cortical transplants on neonatal host thalamus will be examined. One week after removal of the frontal cortex of newborn rats, either fetal frontal cortex, fetal cerebellum, fetal parietal cortex, minced fetal frontal cortex, or gelfoam is transplanted into lesion cavities. Since marked host thalamic atrophy normally occurs ipsilateral to fetal frontal cortex lesions, this will determine which transplants ameliorate the atrophy. Host-transplant connections are examined in the above experiments to determine which effects correlate with formation of connections. Cortex injury due to strokes, head trauma, and other diseases can lead to devastating, permanent motor and sensory impairments in humans. The data from this proposal will help determine whether fetal transplants might offer some hope for treating such deficits.
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