The aim of this research is to isolate and analyze genes that influence the generation and function of specific types of neurons. To accomplish this goal, special features of canaries are exploited: 1) continual production and replacement of neurons throughout the forebrain of adults; 2) well-characterized neuroanatomical loci in the forebrain underlying a learned behavior (song); 3) stimulatory effects of androgens on neurogenesis, song control neuroanatomy, and song learning/production. In preliminary work, the complexity of adult canary forebrain mRNA has been characterized, and cDNAs have been isolated for 8 rare mRNAs that are more abundant in the forebrain than in the nonforebrain. An improved in situ hybridization procedure shows that each of these cDNAs recognizes a different subset of brain cells based on anatomical distribution and morphology. Similar methods are now to be applied to seek clones of mRNAs that are preferentially expressed in cells during adult neurogenesis (i.e., precursors and migrating neuroblasts) or cells actively engaged in the song learning circuitry. To this end, tissues and mRNA will be analyzed and compared from the primary song control nucleus (HVc) including its overlying neurogenic ventricular zone, HVc of androgen-treated ovariectomized females and controls, and canary embryos. Identified clones will by characterized by nucleotide sequence analysis, in situ hybridization studies, and through production of antibodies to encoded peptides. Information and gene probes gained by this strategy may be applied to other species (including man) by isolating homologous sequences through nucleic acid hybridization. These studies may ultimately lead to therapies designed to modify the production or function of specific cell types in human brain.
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