Retinogeniculate (RG) synapses connect retinal ganglion cells to the thalamic relay cells of the dorsal lateral geniculate nucleus (dLGN). They are critical for regulating the flow of visual information from retina to primary visual cortex (V1). RG synapses in dLGN are uniquely larger and stronger than their counterparts in other retinorecipient regions. Moreover, in dLGN, RG synapses can be classified into two groups: simple RG synapses, which contain glia-encapsulated single RTs synapsing onto relay cell dendrites, and complex RG synapses, which contain numerous RTs that converge onto the shared regions of relay cell dendrites. To identify target-derived molecules that direct the transformation of RTs into unique RG synapses in dLGN, I used RNAseq to obtain the whole transcriptome of dLGN and its adjacent retinorecipient nucleus, vLGN, at different time points during RG synapses development. Leucine-Rich Repeat Transmembrane Neuronal 1 (LRRTM1), a synaptogenic adhesion molecule, was the candidate I selected based on its expression pattern. Here, I discovered that LRRTM1 regulates the development of complex RG synapses. Mice lacking LRRTM1 (lrrtm1-/-) not only show a significant reduction in the number of complex RG synapses but they exhibit abnormal visual behaviors. This work reveals, for the first time, a high level of retinal convergence onto dLGN relay cells in thalamus and the functional significance of this convergence for vision. / Ph. D. / Our relationship with the environment is heavily reliant on vision, an intricately wired sensory system, much like a circuit. This circuit begins at the eyes, with the retina, and spreads to different visual centers in the brain. Retinal ganglion cells (RGCs) send their wires, called axons, carrying information about the visual world to over 40 different regions in the brain. A major target of these axons is the dorsal lateral geniculate nucleus (dLGN), a region critical to our ability to perceive the visual world. The sites where RGCs connect to the dLGN cells are called retinogeniculate (RG) synapses, and my studies focused on understanding how these RG synapses develop and how they function. I am the first to discover the fact that more than a dozen distinct RGC axons cluster within the same neighborhood of one shared target cell in the dLGN. Unique to the dLGN, these clusters, termed complex RG synapses, are not seen in any other RGC target regions in the brain. Moreover, I demonstrated a new molecular mechanism that forms these synapses by identifying a protein called LRRTM1, as a critical molecule required for the formation of these complex RG synapses in the dLGN. By studying the visual behavior of mutant mice lacking LRRTM1, I demonstrated that complex RG synapses are important for performing complex visual tasks. The discoveries detailed within this dissertation add to current efforts to restore vision in patients suffering from severe visual impairments, via regenerative therapies, by furthering our understanding of how neural wires connect in the visual circuit to reveal everything we will ever know about the visual world.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/81893 |
| Date | 22 January 2018 |
| Creators | Monavarfeshani, Aboozar |
| Contributors | Biological Sciences, Fox, Michael A., Valdez, Gregorio, Friedlander, Michael J., Moore, Ignacio T., Gourdie, Robert G. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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