Cholinergic Waves Have a Modest Influence on the Transcriptome of Retinal Ganglion Cells.

Area of Science:

• Neuroscience
• Developmental Biology
• Genetics

Background:

• Retinal waves, driven by cholinergic signaling, are crucial for visual system development.
• The β2 subunit of the nicotinic acetylcholine receptor is essential for these waves, and its absence (β2KO mouse) disrupts visual circuit refinement.
• The impact of cholinergic wave disruption on the gene expression of individual retinal ganglion cell (RGC) types is not well understood.

Purpose of the Study:

• To investigate the effects of cholinergic signaling disruption on RGC gene expression at the single-cell level.
• To determine if β2 subunit deficiency impacts RGC differentiation programs and gene expression profiles.
• To identify specific genes and RGC types affected by the absence of cholinergic waves.

Main Methods:

• Single-cell RNA sequencing was performed on RGCs from wild-type and β2KO mice at postnatal day 7.
• Transcriptomic data analysis identified differentially expressed genes in β2KO RGCs.
• In situ hybridization and whole-cell recordings were used to validate findings for specific genes, like *Kcnk9*.

Main Results:

• RGC differentiation programs were unaffected in β2KO mice.
• The overall magnitude of transcriptional changes in RGCs was modest compared to normal maturation.
• Approximately 238 genes showed altered expression in a type-specific manner, including downregulation of *Kcnk9* in αRGCs.
• This contrasts with significant transcriptomic changes observed in downstream visual areas.

Conclusions:

• Cholinergic signaling via retinal waves has a limited transcriptomic impact within the retina itself.
• These waves modulate molecular programs in RGCs in a subtle, type-specific manner, not uniformly.
• The findings highlight the nuanced role of early visual activity in shaping RGC molecular identity.