Determinants of Dendritic Morphology, Connectivity, Spacing and Functional Coverage of Retinal Nerve Cells

Prof. Benjamin Reese

July 23, 2007

Abstract:

My lab has been exploring the determinants of dendritic morphology, connectivity and intercellular spacing that underlie the functional coverage of retinal nerve cell mosaics.Recent studies have focused on the horizontal cells of the retina, being inhibitory interneurons with dendritic fields that overlap one another, contacting the pedicles of cone photoreceptors.Because of their regular spacing, their dendrites provide a uniform coverage of the retinal surface.The developmental mechanisms establishing their intercellular spacing and morphological properties are undefined, but fate-determination events and cell-intrinsic instructions have been suggested to underlie these features. I will consider an alternative hypothesis, that interactions with neighboring cells drive the intercellular spacing and dendritic differentiation of these cells. Using a variety of natural and genetically-modified strains of mice, we have modulated the relationship between horizontal and cone cell number to study the role of homotypic and afferent density upon mosaic patterning and differentiation. A number of spatial statistics for analyzing the patterning of retinal mosaics in 2D will be discussed. Variation in horizontal cell density is shown to produce a corresponding change in the average spacing between horizontal cells and in the size of the dendritic field, while altering cone density leaves dendritic field size unaffected and does not perturb mosaic patterning, but drives higher order dendritic branching and terminal clustering. Afferent and homotypic interactions therefore generate the network properties of horizontal cells that underlie their functional coverage. Such issues have not been addressed within networks of nerve cells within the brain for a variety of reasons, partly because determining such spatial statistics in 3D is computationally demanding, and because of the difficulty in visualizing nerve cell patterning in 3D. At the end of the talk, I will describe the creation of new software tools permitting the analysis and modeling of such nerve cell patterning in three dimensions.