Defense Date

2010

Document Type

Thesis

Degree Name

Master of Science

Department

Anatomy & Neurobiology

First Advisor

Michael Fox

Abstract

In the developing visual system, the axon of a pre-synaptic cell must be guided to a post-synaptic partner. Retinal ganglion cells (RGCs) in the eye are an excellent model to study this process. Multiple classes exist that respond to specific types of light input, and these project to different destinations in the brain that process distinct types of information. The RGC axons that navigate to the lateral geniculate nucleus (LGN) do so in a class-specific manner. Axons from RGCs that mediate non-image forming functions innervate the ventral LGN (vLGN) and the intergeniculate leaflet (IGL). Axons from RGCs that process image-forming information bypass these regions to innervate the dorsal LGN (dLGN). The extracellular protein reelin was identified as a potential factor in RGC axonal targeting of the vLGN and IGL, and the reeler mutant mouse used to study the effects of its functional absence. Anterograde labeling of RGCs and their axons with Cholera toxin B (CTB) revealed reduced patterns of retinal innervation to the vLGN and IGL in mutant mice. Moreover, the absence of functional reelin resulted in axons incorrectly growing into inappropriate regions of the thalamus. We identified these misrouted axons as those of the intrinsically photosensitive RGCs (ipRGCS), a class of RGCs known to project to the affected subnuclei. In contrast to defects in ipRGC targeting, no deficits were seen in retinogeniculate or corticothalamic projections in classes of axons that normally target the dLGN. Immunohistochemistry did not reveal any effects of the absence of the functional reelin on the LGN cytoarchitecture, which is unlike many other brain regions altered in the reeler. In summary, results suggest that intact reelin is required for class-specific retinogeniculate targeting to the vLGN and IGL. The defects are likely to be in targeting and not in neuronal positioning.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2010

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