Contributions of spontaneous retinal activity to the development of segregated eye-specific projections in the ferret visual system

The developmental refinement of eye-specific projections to the dorsal lateral geniculate nucleus (dLGN) and primary visual cortex (V1) are classic model systems for studying mechanisms of neural circuit development in the mammalian brain. Here I describe studies performed while in graduate school that explored the activity-dependent refinement of retinogeniculate and geniculocortical projections in the ferret. I have provided the field with the most comprehensive anatomical map of the developing retinogeniculate projection system in the ferret available to date (Chapter 1). In a separate series of experiments, I contributed to settling a debate about the physiological effects of a particular pharmacological agent, epibatidine (EPI), used widely in the field to disrupt spontaneous retinal activity during retinogeniculate development (Chapter 2). We reported that EPI blocks retinal waves and silences spontaneous spiking in many, but not all, retinal ganglion cells, a conclusion which unifies previously conflicting reports in the field. In other work, I describe the normal development of segregated eye-specific retinogeniculate projections following manipulations that dramatically alter spontaneous retinal activity (Chapter 3). These experiments offer additional constraints on the features of spontaneous retinal activity that may be critical for the refinement of eye-specific retinogeniculate projections. I also show that On/Off sublamination is activity-dependent, but that the On/Off projection system is functionally normal despite activity-manipulations that disrupt On/Off laminae and disrupt expression of an inhibitory signaling molecule, ABAKAN, normal separating these domains (Chapter 4). This work expands upon earlier reports from other groups and demonstrates that ABAKAN is not necessary for the functional development of On/Off channels in the retinogeniculate pathway. Lastly, I reviewed the role of Eph receptor tyrosine kinases and their ligands, the ephrins, in the emergence of afferent and efferent pathways into and out of the thalamus respectively. As an appendix chapter, I contributed to experiments demonstrating a role for spontaneous retinal activity in the development of segregated ocular dominance columns (ODCs) in the primary visual cortex. We showed that disrupting this activity leads to a failure of ODC development anatomically, as well as a dramatic enlargement in the receptive field area of binocular responding cortical neurons.