Retinal waves are required for state-dependent visual processing
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE211406 | GEO | 2026/05/01
REPOSITORIES: GEO
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Project description:Retinal waves are required for state-dependent visual processing
| PRJNA870115 | ENA
Project description:In the early stages of retinal development, a form of correlated activity known as retinal waves causes periodic depolarizations of immature retinal ganglion cells (RGCs). Retinal waves are crucial for refining visual maps in the brain's retinofugal targets and for the development of retinal circuits underlying feature detection, such as direction selectivity. Yet, how waves alter gene expression in immature RGCs is poorly understood, particularly at the level of the many distinct types of RGCs that underlie the retina’s ability to encode diverse visual features. We performed single-cell RNA sequencing on RGCs isolated at the end of the first postnatal week from wild-type (WT) mice and β2KO mice, which lack the β2 subunit of the nicotinic acetylcholine receptor, leading to the disruption of cholinergic retinal waves. Statistical comparisons of RGC transcriptomes between the two conditions reveal a weak impact of retinal waves on RGC diversity, indicating that retinal waves do not influence the molecular programs that instruct RGC differentiation and maturation. Although wave-dependent gene expression changes are modest in the global sense, we identified ~238 genes that are significantly altered in select subsets of RGC types. We focused on one gene, Kcnk9, which encodes the two-pore domain leak channel potassium channel TASK3. Kcnk9, which is highly enriched in αRGCs, was strongly downregulated in β2KO. We validated this result using in situ hybridization and performed whole-cell recording to demonstrate a significant decrease in the leak conductance in β2KO. Our dataset provides a useful resource for identifying potential targets of spontaneous activity-dependent regulation of neurodevelopment in the retina.
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Project description:Retinal ganglion cells (RGCs) are the projection neurons that transmit visual information from the retina to the brain via the optic nerve. A substantial proportion of RGCs are eliminated by programmed cell death during development to regulate their final number, yet how cell death impacts RGC development in human retinas remains poorly understood. Here, we characterized the timing and cell-type-specificity of cell death in human fetal retinas and retinal organoids. We identified two waves of apoptosis: an early wave targeting retinal neuronal precursors and a late wave affecting RGCs and other neurons. In addition to these two waves of apoptosis, organoids displayed a distinct wave of necrosis in the innermost core region that eliminates nearly all RGCs during long-term culture. To investigate the functions of the apoptotic waves during retinal development, we differentiated BAX/BAK double mutant organoids that are deficient for apoptosis. In these mutant organoids, RGC survival was improved, RGC neurogenesis and maturation were delayed, and RGCs were lost through a compensatory increase in necrosis. Our data suggest that the waves of developmental apoptosis promote human RGC neurogenesis and maturation. Together, our results highlight the roles of cell death in human RGC development and the challenges in retinal organoid design. Overcoming these obstacles would improve the utility of retinal organoids for modeling optic neuropathies like glaucoma
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Project description:The formation of the visual system is a complex multistep process that includes the establishment of proper connectivity of retinal ganglion cell (RGC) axon terminals with their relay neurons located in the brain. In mammals, the assembly of the different components of the visual circuit occurs at perinatal stages before eye opening. Upon reaching the target nuclei RGC axons extensively arborize and subsequently refine to establish the final connections. Spontaneous activity generated in the immature retina plays an essential role in the refinement of visual terminals at the main image-forming nuclei (IFN) that follow an eye-specific and retinotopic organization. However, the molecular mechanisms underlying spontaneous activity-dependent axon remodeling, and the influence of this activity in the connectivity of non-image forming nuclei (NIFN) that lack precise retinotopic maps and/or eye-specific segregation, are not well known. Here, by generating conditional mice with disturbed spontaneous retinal aneactivity and analyzing their retinal transcriptomic profiles, we identified novel players involved in axon refinement at the visual nuclei (e. g. Syt13). The analysis of visual projections in the NIFN of these mice revealed that correlated-retinal activity shapes final connectivity in non retinotopic or eye-specific segregating visual nuclei.
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Project description:Mature cortical sensory areas are specialized to process unique sensory stimuli. Recent evidence shows that in the mouse embryo sensory cortices are prepared to respond to an incoming input from the periphery. However, whether these sensory circuits originate as modality specific modules, or they are segregated over time remains unknown. Here, we demonstrate that visual and somatosensory circuits originate as functionally intermingled modules, as whisker-pad stimulations at prenatal life led to a multimodal response activating both primary visual and somatosensory cortices. This multimodal response is switched to unimodal at birth via the superior colliculus, a midbrain structure where both modalities converge. Retinal afferent to the superior colliculus prompts the gating of visual from somatosensory circuits achieving sensory modality specificity at birth. Blocking stage I retinal waves resulted in prolonged convergence of somatosensory and visual circuits at the superior colliculus, which led to long-term consequences in the molecular identity of the superior colliculus and caused defects in eye-specific segregation and retinotopy. Hence, the superior colliculus stands as a key developmental regulator of sensory circuits by channeling modality stimuli to their appropriate sensory pathway.
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Project description:Rbfox1 is a splicing regulator that has been associated with various neurological conditions such as autism spectrum disorder, mental retardation, epilepsy, attention-deficit/hyperactivity disorder, and schizophrenia. We show that in adult rodent retinas, Rbfox1 is expressed in all types of retinal ganglion cells (RGCs) as well as in certain subsets of amacrine cells (ACs) within the inner nuclear and ganglion cell layers. In developing retinas, Rbfox1 can be detected as early as E12. At that age, Rbfox1 is localized in the cytoplasm of differentiated RGCs. Between P0 and P5, strong expression of Rbfox1 in the inner plexiform layer was observed. This coincided with switching of Rbfox1 localization in RGC somas from cytoplasmic to a predominantly nuclear. Dynamic changes in Rbfox1 expression during first 10 postnatal days are correlated with the stage II spontaneous retinal waves of excitation, which in mice begins around the time of birth and continues for as long as two weeks. By P10, dendritic staining of Rbfox1 was dramatically reduced and remained so in the fully developed retina. In Rbfox1 knockout (KO) animals no detectable changes in retinal gross morphology were observed two months after Rbfox1 downregulation. However, the visual cliff test revealed marked abnormalities of depth perception of these animals. Retinal transcriptome analysis of Rbfox1 KO mice identified a number of genes that are involved in establishing neural circuits and synaptic transmission, including Vamp1, Vamp2, Snap25, Trak2, and Slc1A7, suggesting a role of Rbfox1 in the regulation of genes that facilitate AC and RGC synaptic communication.
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