The overall hypothesis of the Program Project is that SIDS is due to developmental abnormalities of the ventral medulla that interfere with protective cardiorespiratory responses to potentially life-threatening, but often occurring, events during sleep, such as hypoxia, hypercapnia, and apnea. In the context of the Program Project, Project IV will attempt to characterize the cyto-and chemoarchitecture of the ventral medulla of the piglet and human infant. The over-riding concept of the project is that the ventral medullary surface contains clusters of small neurons that are cytologically and neurochemically homogenous and thus form a unified class of neurons; and that his class of neurons provides a common influence on autonomic modulation, chemoreception, and cardiopulmonary coupling, although the specific role of each cluster of neurons varies in accordance with its specific somatotopic connections. First, we will test the hypothesis that, in the piglet, the small ventral neurons of the raphe pallidus, the most superficial parapyramidal neurons, and the retrotrapezoid neurons, belong to the unified class of neurons as evidenced by being cytoarchitectonically identical and expressing the same neurotransmitters and neurotransmitter receptors. Second, we will test the hypothesis that, based on cytoarchitectonic and chemoarchitectonic criteria, the human arcuate nucleus is homologous to the small ventral neurons of the piglet raphe pallidus, the piglet superficial parapyramidal nucleus, and the piglet retrotrapezoid nucleus. We will employ the traditional approach of comparative neuroanatomy by testing if neurons in both species share common cell morphology, express common receptors and share common immunohistochemical staining characteristics. Morphologic studies will employ Neurobiotin/R and standard staining methods; autoradiographic studies will test for expression for receptors for glutamate, serotonin, GABA, somatostatin, and acetylcholine (muscarinic); immunohistochemical studies will test for expression of choline acetyltransferase, tyrosine hydroxylase, glutamate decarboxylase, glutamate, substance P, cholecystokinin, and thyrotropin releasing hormone. It is goal of Project IV to develop a comparative anatomic framework that will help the physiologic studies in Projects I-III shed light on the potential significance of arcuate nucleus abnormalities reported in SIDS victims. Ultimately, this neuroanatomic framework may be useful to establish a model for SIDS in the developing piglet based on impaired behavioral and ventilatory responses to asphyxial rebreathing induced by dysfunction of the piglet arcuate homologue.
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