The aim of this project is to isolate the neurobiological mechanism responsible for sensory gating in transplants of brain tissue from dead human fetuses into the anterior chamber of the eye of rat hosts. The tissue will be obtained during routine abortions, appropriate brain areas will be dissected, and the graft will be placed into the anterior chamber of the eye of an athymic nude rat. There the fetal tissue increases in size and differentiates so that neurons are formed. These human neurons can then be studied with standard neurobiological techniques usually reserved for animal models, including extracellular and intracellular single neuron recording, pharmacology with specific agonists and antagonists, in vivo electrochemistry, and a variety of histological procedures. Some of the tissue will be obtained from abortions of women with schizophrenia; in co-operation with project 2, linkage studies will be performed to assess whether the tissue is likely to carry genes which convey increased risk for schizophrenia.
We aim to determine if specific neurobiological deficits which would account for the deficit in sensory gating can be found in those particular specimens. Initial studies will be focused on the hippocampus, but, working with projects 3 and 4, we will concentrate on areas shown to be the most likely candidates for the neurobiological substrate of sensory gating. Using the in oculo transplants we can study single brain areas or, by transplanting two areas, we can generate synaptic connections between two different brain regions.
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