Many recent studies, including work in the applicant's laboratory, have demonstrated that neurotransmitter expression is responsive to environmental influences both in regard to establishment of phenotype during development and in regard to regulation of synthesis and resting levels of neuroactive substances int the mature nervous system. These observations have heightened awareness that the regulation of transmitter expression would be a powerful mechanism through which experience could shape the basic physiological properties of neuronal circuits. The long-term goal of the research proposed here is to evaluate the involvement of the regulation of neurotransmitter/neuropeptide expression by physiological activity in the development of discriminative and memorial capacities in the olfactory system. The immediate goals of the research proposed are to use immunohistochemical and in situ hybridization techniques to evaluate the development of neuroactive substances in different populations of main olfactory bulb (MOB) neurons and test how the emerging pattern is influenced by odor deprivation and early learning experiences. Specifically studies are proposed to: 1) Describe the ontogenetic appearance of immunoreactivities to several neuroactive peptides, indices of classical neurotransmitters, and calcium binding proteins in neurons of the MOB; 2) conduct colocalization studies to identify the neurochemical characteristics which define distinct subpopulations of periglomerular cells and examine whether these restrictive phenotypes arise early during development of whether these morphologically homogeneous neurons first exhibit broad (inclusive) phenotypic characters which input on the expression of putative neurotransmitters in developing and adult rat MOB; and 4) Assess the effects of learning at different ages on the expression of neuroactive substances in subpopulations of MOB neurons. The proposed studies should provide new information as to how the development of the central nervous system might be shaped by sensory stimulation and experience.
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