Experiments are proposed to investigate the role of abnormal early experience in producing abnormal neural pathways linking the left and right hemispheres of the brain. The interhemispheric pathway matures quite late during development, and its pattern of development is particularly interesting. There is an initial over-production of connections (mistakes?) followed by a gradual narrowing of the zone containing neurons which send axons to the opposite hemisphere. This narrowing process can be altered when there is unusual experience, resulting in persistence of developmental mistakes, which could provide a substrate for abnormal behavior. We will use anatomical techniques involving retrograde transport of horseradish peroxidase and anterograde transport of isotope to address a number of questions related to the role of abnormal experience in producing abnormal interhemispheric pathways. We will use a model system chosen to allow complete control of early experience. In addition, the anatomy and physiology of the interhemispheric pathway are well understood in this system. The goal of the experiments is to increase our understanding of the link between abnormal early experience and abonormal behavior. It has been known for many years that abnormal experience in childhood can result in severe mental health problems in adulthood. Since abnormal experience can result in retention of developmental mistakes in brain connectivity, this link may form a structural basis of many psychiatric disorders. Interhemispheric pathways may be particularly vulnerable to abnormal early experience. Indeed, recent computed tomography studies of schizophrenic patients have shown that they have a high incidence of abnormal hemispheric specialization. The proposed experiments will explore the circumstances and mechanism for retention of developmental mistakes in interhemispheric connectivity resulting from abnormal early experience.
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