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In the visual system, retinal axons convey visual information from the outside world to dozens of distinct retinorecipient brain regions and organize that information at several levels, including either at the level of retinal afferents, cytoarchitecture of intrinsic retinorecipient neurons, or a combination of the two. Two major retinorecipient nuclei which are densely innervated by retinal axons are the dorsal lateral geniculate nucleus, which is important for classical image-forming vision, and ventral LGN (vLGN), which is associated with non-image-forming vision. The neurochemistry, cytoarchitecture, and retinothalamic connectivity in vLGN remain unresolved, raising fundamental questions of how it receives and processes visual information. To shed light on these important questions, used in situ hybridization, immunohistochemistry, and genetic reporter lines to identify and characterize novel neuronal cell types in mouse vLGN. Not only were a high percentage of these cells GABAergic, we discovered transcriptomically distinct GABAergic cell types reside in the two major laminae of vLGN, the retinorecipient, external vLGN (vLGNe) and the non-retinorecipient, internal vLGN (vLGNi). Furthermore, within vLGNe, we identified transcriptionally distinct subtypes of GABAergic cells that are distributed into four adjacent sublaminae. Using trans-synaptic viral tracing and in vitro electrophysiology, we found cells in each these vLGNe sublaminae receive monosynaptic inputs from retina. These results not only identify novel subtypes of GABAergic cells in vLGN, they suggest the subtype-specific laminar distribution of retinorecipient cells in vLGNe may be important for receiving, processing, and transmitting light-derived signals in parallel channels of the subcortical visual system.

In the visual system, retinal axons convey visual information from the outside world to dozens of distinct retinorecipient brain regions and organize that information at several levels, including either at the level of retinal afferents, cytoarchitecture of intrinsic retinorecipient neurons, or a combination of the two. Two major retinorecipient nuclei which are densely innervated by retinal axons are the dorsal lateral geniculate nucleus, which is important for classical image-forming vision, and ventral LGN (vLGN), which is associated with non-image-forming vision. The neurochemistry, cytoarchitecture, and retinothalamic connectivity in vLGN remain unresolved, raising fundamental questions of how it receives and processes visual information. To shed light on these important questions, used in situ hybridization, immunohistochemistry, and genetic reporter lines to identify and characterize novel neuronal cell types in mouse vLGN. Not only were a high percentage of these cells GABAergic, we discovered transcriptomically distinct GABAergic cell types reside in the two major laminae of vLGN, the retinorecipient, external vLGN (vLGNe) and the non-retinorecipient, internal vLGN (vLGNi). Furthermore, within vLGNe, we identified transcriptionally distinct subtypes of GABAergic cells that are distributed into four adjacent sublaminae. Using trans-synaptic viral tracing and in vitro electrophysiology, we found cells in each these vLGNe sublaminae receive monosynaptic inputs from retina. These results not only identify novel subtypes of GABAergic cells in vLGN, they suggest the subtype-specific laminar distribution of retinorecipient cells in vLGNe may be important for receiving, processing, and transmitting light-derived signals in parallel channels of the subcortical visual system.

Inhibitory interneurons comprise a fraction of the total neurons in the visual thalamus but are essential for sharpening receptive field properties and improving contrast-gain of retinogeniculate transmission. During early development, these interneurons undergo long-range migration from germinal zones, a process regulated by the innervation of the visual thalamus by retinal ganglion cells. Here, using transcriptomic approaches, we identified a motogenic cue, fibroblast growth factor 15 (FGF15), whose expression in the visual thalamus is regulated by retinal input. Targeted deletion of functional FGF15 in mice led to a reduction in thalamic GABAergic interneurons similar to that observed in the absence of retinal input. This loss may be attributed, at least in part, to misrouting of interneurons into nonvisual thalamic nuclei. Unexpectedly, expression analysis revealed that FGF15 is generated by thalamic astrocytes and not retino-recipient neurons. Thus, these data show that retinal inputs signal through astrocytes to direct the long-range recruitment of interneurons into the visual thalamus.

Unconventional collagens are nonfribrillar proteins that not only contribute to the structure of extracellular matrices but exhibit unique bio-activities. Although roles for unconventional collagens have been well-established in the development and function of non-neural tissues, only recently have studies identified roles for these proteins in brain development, and more specifically, in the formation and refinement of synaptic connections between neurons. Still, our understanding of the full cohort of unconventional collagens that are generated in the mammalian brain remains unclear. Here, we sought to address this gap by assessing the expression of transmembrane collagens (i.e., collagens XIII, XVII, XXIII and XXV) in mouse brain. Using quantitative PCR and in situ hybridization (ISH), we demonstrate both region- and cell-specific expression of these unique collagens in the developing brain. For the two most highly expressed transmembrane collagens (i.e., collagen XXIII and XXV), we demonstrate that they are expressed by select subsets of neurons in different parts of the brain. For example, collagen XXIII is selectively expressed by excitatory neurons in the mitral/tufted cell layer of the accessory olfactory bulb (AOB) and by cells in the inner nuclear layer (INL) of the retina. On the other hand, collagen XXV, which is more broadly expressed, is generated by subsets of excitatory neurons in the dorsal thalamus and midbrain and by inhibitory neurons in the retina, ventral thalamus and telencephalon. Not only is col25a1 expression present in retina, it appears specifically enriched in retino-recipient nuclei within the brain (including the suprachiasmatic nucleus (SCN), lateral geniculate complex, olivary pretectal nucleus (OPN) and superior colliculus). Taken together, the distinct region- and cell-specific expression patterns of transmembrane collagens suggest that this family of unconventional collagens may play unique, yet-to-be identified roles in brain dev