Afferent regulation of mitral cell phenotype

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Developmental regulation of mitral cell glomerulization and integrative properties will be addressed by integrated anatomical, physiological and molecular biological approaches. The first aim is to determine the time course of the development of bistability and LLD, two important integrative properties of mature mitral cell dendrites. Potassium channels that mediate bistability will be identified and their developmental expression documented. A related goal is to determine when voltage gated K channel and GluR receptor genes are expressed in relation to development of glomerularization, bistability and LLDs. The second aim is to test whether LLDs, bistability and glomerularization are regulated by afferent odor-evoked activity. To accomplish this, knockout mice lacking elements in their odor transduction cascade and, as a consequence, lacking patterned glomerular activity, will be examined, together with stimulus deprived mice, for predicted disruption of glomerularization and delayed or prevented development of integrative properties. The third aim is to evaluate the role that functional activation of a single immature apical dendrite may play in "capturing" that one to the exclusion of others in the process of glomerularization. This work will use focal, laser-released caged glutamate for focal activation of a dendrite in culture. Related experiments will examine whether activation of one dendrite results in the non-activated ones becoming refractory to stimulation leading, in turn, to their elimination. The fourth aim tests the hypothesis that glomerulization by a single mitral cell dendrites is regulated by activity induced gene expression. Analysis of expression of BMP secreted macromolecules will be performed and a determination made of whether they are released in an activity-dependent manner during activation of olfactory nerve inputs. Possible functions of these molecules in the glomerulization process will be assessed in molecular blocking experiments.