Cells, circuits, and development of the mouse lateral geniculate nucleus

Abstract

In the visual system, retinal axons transmit visual information from external stimuli to numerous and distinct brain regions. In rodents, one major area that is densely innervated by retinal input is the visual thalamus. The mouse visual thalamus serves as a powerful model system to understand sensory circuit development based on its orderly structure and ease of accessibility for experimental manipulation. Within the visual thalamus, the lateral geniculate nucleus (LGN) is divided into three distinct regions: ventral LGN (vLGN), dorsal LGN (dLGN), and the intergeniculate leaflet (IGL). Previous studies have characterized the cytoarchitecture and circuitry of dLGN, which is crucial for classical image-forming vision. However, the molecular resolution of subtypes and the connection between subtypes of retinal ganglion cells with those cell types in dLGN remains unresolved. vLGN is known to be associated with non-image-forming vision, though its complete neurochemistry, cytoarchitecture, and afferent and efferent circuitry remain unresolved, raising fundamental questions about its functional role within the visual system. Identifying the structure and function of neural circuits related to vision is crucial for understanding how light exerts its influence on programming an individual's circadian cycle, mood disorders, fear perception, and perception and interaction with the environment. We employed state-of-the-art single-nucleus sequencing to identify a comprehensive list of cells in both dLGN and vLGN. Using this knowledge, we next explored the development of cell-type specific layers in the vLGN. In situ hybridization, immunohistochemistry, and genetic reporter lines revealed that the subtype-specific layering of retinorecipient cells in vLGNe is established during embryonic development. Taken together, the studies in this dissertation have not only identified novel subtypes of dLGN and vLGN cells but 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 LGN receives, processes, and transmits light-derived signals in the visual system. Elucidating these pathways gives potentially generalizable principles in how sensory information is organized in the brain.