Date of Award

2-11-2008

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Charles A. Greer

Abstract

Correct targeting and differentiation of the mitral cell (MC) dendrites in the olfactory bulb (OB) is clearly essential for development of functional neuronal circuits. MCs, the primary OB projection neurons, receive odor information from OSN axons via axodendritic synapses on their apical dendrite; the signal is further processed via dendrodendritic synapses on MC lateral dendrites. In the adult, each MC cell apical dendrite targets a single glomerulus, ending in a characteristic glomerular tuft and receiving input from molecularly defined subsets of OSNs. MC lateral dendrites segregate deep to the glomerular layer, in a sublamina of the external plexiform layer. MC dendrites are initially undifferentiated and often supernumerary; the adult form of one apical and several lateral dendrites emerges postnatally. We sought to define more clearly the emergence of MC apical versus lateral dendrites using DiI fills. We also used a dendritic growth cone specific antibody, CDA 1 to assess spatiotemporal patterns of development in the OB. MCs progressed through a broad spectrum of transitional morphologies from a broadly spread arbor of supernumerary dendrites in the embryo to the single apical dendrite and lateral dendrites characteristic of the adult. At P0, MCs exhibit the immature dendritic morphology with a broadly spread arbor of a large number of relatively uniform dendrites. By P1, this arbor appears to have narrowed and one dendrite appears thicker than the others, probably on its way to differentiating into an apical dendrite. At P4, two clearly distinguishable subpopulations of neurons have clearly emerged, but some cells exhibit two apical dendrites. By P8, MCs appear to have an adult dendritic morphology. Quantitative analysis of CDA 1 expression patterns in the OB at postnatal day 0, 2, 4, 8, suggests intra- and interlaminar patterns of dendritic development. Preliminary data further suggest distinct temporal windows of MC dendritic development along the rostrocaudal axis. CDA 1 expression in all laminae decreases significantly by postnatal day 8 and appears indistinguishable from background in the adult. Thus, both lines of data show evidence of significant postnatal dendritic remodeling.

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This is an Open Access Thesis.

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