ONTOGENY OF FOREBRAIN DOPAMINE RECEPTORS

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The PI will learn the following with the support of this award: in situ hybridization using probes for D2, D3 and D4 dopamine receptor subtypes in conjunction with Northern blot analysis of brain-extracted mRNA; immunohistological techniques to identify cell populations corresponding with the areas of ligand binding or probe hybridization; and, a detailed knowledge of the gross and microscopic neuroanatomy of the developing human brain. These acquired skills will be used to complement the findings of work-in-progress characterizing the ontogeny of [3H]-YM 09151-2 binding in human fetal brain tissue using receptor autoradiography. The PI's newly acquired skills will be applied to the following specific projects using tissues obtained from the Central Laboratory for Human Embryology at the University of Washington: 1) characterization of the ontogeny of dopamine receptors in human forebrain using quantitative receptor autoradiography to identify gross and micro- neuroanatomic distributions of specific binding; 2) comparison of the distribution of cell-surface dopamine receptors to the distribution of D2, D3 and D4 dopamine receptor message using in situ hybridization; 3) identification of the cell populations which express dopamine receptors (phenotype and/or message) int he forebrain during early-to-middle gestation using appropriate histological techniques; 4) clarification of the relationship of subplate neurons (identified by NGFR immunohistochemistry) to cell populations which express dopamine receptors; and 5) identification, in a pilot project, specific tissue specimens considered at risk for congenital brain anomaly to compare to tissues without such risk. The supervised research experience provided by this award will enable the PI to characterize the "normal" ontogeny of human forebrain dopamine receptors.