UCSF

Connections between sensory areas are often organized using topographic maps, which preserve in the target the neighbor-neighbor relations present in the source. In this dissertation, I use functional imaging, anatomical tracing, and computational modeling to investigate how neural activity and molecular guidance cues interact during neural development to form orderly, precise topographic maps.

The first chapter describes the role of EphB/ephrin-B signaling in shaping topographic maps in the superior colliculus (SC) and primary visual cortex (V1). These molecules have been widely hypothesized to pattern the SC's elevation axis. Functional imaging of EphB signaling mutants did not reveal disruptions in map precision in either area. However, I found changes in the rotation of the maps, suggesting a role for EphB signaling in specifying the overall axes of the map.

The second chapter details the development of the projection from V1 to the SC. In wildtype animals, the corticocollicular projection aligns with the SC's retinotopic map. We use the Isl2-EphA3^ki/ki mouse, which has a single map of space in V1 and a doubled map in SC, to show that retinal activity early in life is instructive for the proper alignment of this projection.

In the third chapter, we show that the Isl2-EphA3^ki/ki mutant has a single instead of a doubled cortical map because the projection from the retina to the dorsolateral geniculate nucleus contains only a single map of space.

The fourth chapter reveals unexpected heterogeneity in the functional collicular maps of the Isl2-EphA3^wt/ki mutant. We show that the EphA levels of this animal are such that it exists at a point of instability, where stochastic processes during development can push map formation locally into one of two structures. Patterned retinal activity, which encourages the maps to be smooth, is necessary for expressing this variability. We propose a general model for how EphA signaling and retinal activity interact in collicular mapping.

Overall, these results illustrate how functional imaging can reveal unexpected aspects of topographic map development. They show that together, neural activity and molecular guidance cues shape many of aspects of map formation in several different visual brain areas.