Axons of retinal ganglion cells (RGCs) send visual information to a number of retinorecipient regions in the brain. In rodents, visual thalamus receives dense innervations from RGC axons and is important for both image-forming and nonimage-forming visual functions. Retinal inputs invade visual thalamus during embryonic development, before the arrival of non-retinal inputs (such as local interneurons and axonal inputs from other brain regions). In this dissertation, I explore how early innervation of RGC axons affects circuitry in visual thalamus and the role of visual experience, neural activity, and molecular cues in the development.
While the development of astrocytes in cortex has been well-described, they have been largely overlooked in visual thalamus. Using immunohistochemical, functional, and ultrastructural analysis, I show that astrocytes in visual thalamus reach adult-like morphological properties and functionality at retinogeniculate synapses early in development, by eye-opening and before visual experience. These studies reveal that while experience-dependent visual activity from RGC axons is critical for many aspects of visual thalamus development, astrocytic maturation occurs independent of that information about our visual environment.
As with astrocytes, little progress has been made in understanding the development of interneurons in the visual thalamus. Here, I show that retinal inputs interact with thalamic astrocytes to influence the recruitment of GABAergic interneurons into visual thalamus. I found that this interaction between RGC axons and astrocytes is not dependent on neural activity of RGCs. Using transcriptomic analysis, in situ hybridization, and reporter lines, I observed thalamus-projecting RGCs express SHH and astrocytes in visual thalamus express SHH signaling molecules. My results reveal that SHH signaling between RGC axons and astrocytes is critical for astrocytic fibroblast growth factor 15 (FGF15) expression in developing visual thalamus. Ultimately, FGF15 serves as a potent motogen that is essential for thalamic interneuron migration. These data identify a novel morphogen-dependent and activity-independent mechanism that mediates crosstalk between RGCs and astrocytes to facilitate the recruitment of interneurons into the developing visual thalamus. / Doctor of Philosophy / The most dominant sense in human is the sight, which we need to interact with our environment efficiently. The retina takes up the information about our visual world and sends it to the brain, which ultimately puts everything together, for us to see properly. The visual information from the retina goes to the brain via nerves (which are essentially cables/wires of brain cells). These nerves from the retina go to many places in the brain, including a region called visual thalamus, which is the focus of my PhD work. For the past five years, I have been trying to understanding if nerves from the retina play a role in the brain formation during early development. To study this, I have used mice as a model system, as their brain regions that process visual information have very similar structural architecture to those in humans. My research shows that retinal nerves are indeed important for the development of visual thalamus. Here, I show that information from the eye is critical for migration (a process during development where brain cells move from their place of origin to their final location) of cells in visual thalamus. Discoveries made in this dissertation are important because they highlight how different cells in the central nervous system communicate with each other at the level of molecules and how these interactions are important for building circuits that are important for vision.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/110396 |
| Date | 01 June 2022 |
| Creators | Somaiya, Rachana Deven |
| Contributors | Graduate School, Fox, Michael A., Robel, Stefanie, Friedlander, Michael J., Valdez, Gregorio, Farris, Shannon |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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