In the visual system, retinal axons convey visual information from the outside world to dozens of distinct retinorecipient brain regions. In rodents, two major areas that are densely innervated by this retinal input are the dorsal lateral geniculate nucleus (dLGN) and ventral lateral geniculate nucleus (vLGN), both of which reside in the thalamus. The dLGN is well-studied and known to be important for classical image‐forming vision. The vLGN, on the other hand, is associated with non‐image‐forming vision and its neurochemistry, cytoarchitecture, and retinothalamic connectivity all remain unresolved, raising fundamental questions of its role within the visual system. Here, we sought to shed light on these important questions by studying the cellular and extracellular landscape of the vLGN and map its connectivity with the retina. Using bulk RNA sequencing and proteomics, we identified extracellular matrix proteins that form two molecularly distinct types of perineuronal nets in two major laminae of vLGN: the retinorecipient external vLGN (vLGNe) and the non‐retinorecipient internal vLGN. Using in situ hybridization, immunohistochemistry, electrophysiology, and genetic reporter lines, we found that vLGNe and vLGNi are also composed of diverse subtypes of neurons. In vLGNe, we discovered at least six transcriptionally distinct subtypes of inhibitory neurons that are distributed into distinct adjacent sublaminae. Using trans‐synaptic viral tracing and ex vivo electrophysiology, we found that cells in each these sublaminae receive direct inputs from retina. Lastly, by genetically removing visual input, we found that the organization of these sublaminae is dramatically disrupted, suggesting a crucial role for sensory input in the cytoarchitectural maintenance of the vLGN. Taken together, these results not only identify novel subtypes of vLGN cells, but they also point to new means of organizing visual information into parallel pathways – by anatomically creating distinct sensory channels. This subtype-specific organization may be key to understanding how the vLGN receives, processes, and transmits light‐derived signals in the subcortical visual system. / Doctor of Philosophy / As you look around, even as you read this abstract, your retinas are constantly taking in light, converting it into neural signals, and parsing it into different types of visual features. Those light-derived signals are then transmitted from the eye to dozens of brain areas through the optic nerve. Each of these brain areas is important for specialized visual functions. One of the most major visual areas is a region in the thalamus known as the ventral lateral geniculate nucleus (vLGN). Unlike the type of vision we typically think of which involves "seeing" an image, the vLGN primarily receives non-image-forming visual information from the eye which is important for a whole host of light-derived behaviors that do not involve image forming vision. These non-image-forming functions can impact things ranging from jet lag to eye movement to mood disorders and depression. Yet, despite the dense amount of visual information it receives, and the connections it has with many other brain regions, the vLGN has been largely understudied over the years, leaving many fundamental questions unanswered. Here, we unmasked the molecular and cellular landscape of the vLGN and discovered a rich and diverse set of neuronal cell types in this region. Further, by simultaneously labeling these neuronal types, we found that they stratify into their own layers, revealing a striking level of organization which suggests that the vLGN organizes visual information into parallel channels. These discoveries are important because understanding the composition and structure of the vLGN paves the way to understanding how it receives, processes, and transmits sensory signals in the visual system.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/116675 |
| Date | 28 May 2021 |
| Creators | Sabbagh, Ubadah |
| Contributors | Graduate School, Fox, Michael A., Pan, Yuchin Albert, Thompson, Christopher, Clinton, Sarah |
| 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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