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ABSTRACT The retinotectal projection, the direct synapse between retinal ganglion cells (RGCs) of the eye and tectal neurons of the optic tectum, is a major component of the amphibian visual system. A model of circuit formation, this projection has been studied in detail. There are, however, other retinorecipient targets that also comprise the amphibian visual system such as the pretectum and ventral midbrain tegmentum. Understanding how these other components of the visual system form and function will lead to a more comprehensive understanding of how the visual system, as a whole, assembles and functions. Toward this aim, here we describe the functional development of theXenopustadpole accessory optic system (AOS), a direct synaptic connection between RGC axons and the basal optic nucleus of the midbrain tegmentum. The AOS is highly conserved across vertebrates. It functions as the sensory side of the optokinetic and optomotor reflexes, compensatory eye and body movements, respectively, that stabilize the visual scene as the organism moves through it. Using an isolated brain preparation and whole‐cell electrophysiological approaches, we compared the development of the AOS and retinotectal projection. We found that these two retinofugal projections display distinct developmental programs, which appear to mirror their different functions. Retinotectal synapses moved through a dynamic phase of previously described NMDA receptor‐dependent refinement, a process that is known to sharpen the retinotopic map and thereby visual acuity. In contrast, the AOS synapse appeared more stable and activity independent across development, indicative of a hardwired circuit, built to support reflexive optic behaviors.
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This content will become publicly available on February 27, 2026
Cholinergic Waves Have a Modest Influence on the Transcriptome of Retinal Ganglion Cells
In the early stages of development, correlated activity known as retinal waves causes periodic depolarizations of retinal ganglion cells (RGCs). The β2KO mouse, which lacks the β2 subunit of the nicotinic acetylcholine receptor, serves as a model for understanding the role of the cholinergic waves. β2KO mice have disruptions in several developmental processes of the visual system, including reduced retinotopic and eye-specific refinement of RGC axonal projections to their primary brain targets and an impact on the retinal circuits underlying direction selectivity. However, the effects of this mutation on gene expression in individual functional RGC types remain unclear. Here, we performed single-cell RNA sequencing on RGCs isolated at the end of the first postnatal week from wild-type and β2KO mice of either sex. We found that in β2KO, the programs governing RGC differentiation were not impacted and the magnitude of transcriptional changes was modest compared with those observed during 2 d of normal postnatal maturation. This contrasts with the substantial transcriptomic changes seen in downstream visual system areas under wave disruption in recent studies. Overall, we identified ∼238 genes whose expression was altered in a type-specific manner. We confirmed this result via in situ hybridization and whole-cell recording by focusing on one of the downregulated genes in αRGCs,Kcnk9, which encodes the two-pore domain leak potassium channel TASK3. Our study reveals a limited transcriptomic impact of cholinergic signaling in the retina, and instead of affecting all RGCs uniformly, these waves show subtle modulation of molecular programs in a type-specific manner.
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- Award ID(s):
- 2309039
- PAR ID:
- 10617354
- Publisher / Repository:
- DOI PREFIX: 10.1523
- Date Published:
- Journal Name:
- The Journal of Neuroscience
- Volume:
- 45
- Issue:
- 35
- ISSN:
- 0270-6474
- Format(s):
- Medium: X Size: Article No. e0165252025
- Size(s):
- Article No. e0165252025
- Sponsoring Org:
- National Science Foundation
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