Defense Date

2012

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Neuroscience

First Advisor

William Guido

Abstract

The visual system is one of the most widely used and best understood sensory systems and the dorsal lateral geniculate nucleus (dLGN) of the mouse has emerged as a model for investigating the cellular and molecular mechanisms underlying the development and activity-dependent refinement of sensory connections. Thalamic organization is highly conserved throughout species and the dLGN of the mouse possesses many features common to higher mammals, such as carnivores and primates. Two general classes of neuron are present within the dLGN, thalamocortical relay cells and interneurons, both of which receive direct retinal input. Axons of relay cells exit dLGN and convey visual information to layer IV of cortex, whereas interneurons are involved in local circuitry. In addition, dLGN receives rich nonretinal input from numerous areas of the brain. Studies thus far have focused on the retinogeniculate pathway and the development of connections between retinal ganglion cells (RGCs) and relay cells has been well characterized. However, there are still a number of unanswered questions about circuit development in dLGN. Here we examined two aspects that are not well understood, the pattern of retinal convergence onto interneurons and the structural and functional innervation of nonretinal projections. To address the first issue we conducted in vitro whole-cell recordings from acute thalamic slices of GAD67-GFP mice, a transgenic strain in which dLGN interneurons express GFP. We also did 3-D reconstructions of biocytin-labeled interneurons using multi-photon laser scanning microscopy in conjunction with anterograde labeling of retinogeniculate projections to examine the distribution of retinal contacts. To begin to examine the development of nonretinal connections in dLGN we made use of a transgenic mouse (golli-τ-GFP) to visualize corticogeniculate projections, one of the largest sources of nonretinal input to dLGN. Using this mouse we studied the timing and patterning of corticogeniculate innervation in relation to the development of the retinogeniculate pathway. We also used binocular enucleation and genetic deafferentation to test whether the retina plays a role in regulating nonretinal innervation. We found that there is a coordination of retinal and nonretinal innervation in dLGN. Projections from the retina were the first to innervate and they entered dLGN at perinatal ages. They also made functional connections with both relay cells and interneurons at early postnatal ages. Interestingly, relay cells underwent a period of retinogeniculate refinement, whereas the degree of retinal convergence onto interneurons was maintained. This possibly reflects the different roles that these two cell types have in dLGN. Both structural and functional corticogeniculate innervation was delayed in comparison and occurred postnatally, however in the absence of retinal input the timing of corticogeniculate innervation was accelerated. RGCs transmit the visual information encoded in the retina to dLGN so it may be necessary for these connections to be formed before those from nonretinal projections, which serve to modulate that signal on its way to cortex. Thus precise timing of retinal and nonretinal innervation may be important for the appropriate formation of connections in the visual system and the retina seems to be playing an important role in regulating this timing.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

4-23-2012

Included in

Neurosciences Commons

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