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Onkar S Dhande, Ann H Phan, Tania A Seabrook, Phong L Nguyen, Jack T Wang, Andrew Huberman; Developmental mechanisms for establishing functional non-image-forming visual circuits. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1615.
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© ARVO (1962-2015); The Authors (2016-present)
The ability to reflexively adjust the aperture of the eye, termed pupillary light reflex (PLR), is critical for optimizing image quality over a wide range of lighting conditions. The olivary pretectal nucleus (OPN) is a key center in the brain that integrates visual information from multiple functionally distinct types of retinal ganglion cells (RGCs) in order to drive appropriate PLR behaviors. However, how this PLR circuitry is assembled during development and the causal relationships between specific RGC types and PLR behavior remains unresolved.
To identify factors that play an important role in the formation of the PLR circuitry we used a microarray-based approach to assay and compare the genetic profile of transgenically-labeled OPN projecting RGCs to other RGC subtypes including direction selective and alpha RGCs. To study the role of candidate factors identified from the microarray screen we used the Cre/loxP system to generate mutant mice. Using a combination of modern anatomical and quantitative behavioral assays we probed the role of these candidate factors in establishing the different parallel pathways innervating the OPN and investigated their contribution to various aspects of PLR behavior.
We found transcripts for Tbx20, a T-box family transcription factor whose function in the nervous system is relatively unknown, are highly enriched in the different RGC types feeding the OPN. Loss of Tbx20 results in substantial reduction in retinal input to the OPN, which surprisingly did not significantly alter PLR behavior as tested at 10,000 lux with a 490nm LED source [% Constriction (mean ± s.e.m.) Control: 94.9 ± 0.6, n=9; Tbx20 mutant: 92.3 ± 0.75, n=10, p=0.5, one-way ANOVA]. However, when we removed Tbx20 together with the gene encoding the photopigment Melanopsin we observed a severe defect in the PLR (Melanopsin/Tbx20 mutants: 59.5 ± 2.2, n=6, p<0.0001).
Our results reveal that Tbx20 is preferentially expressed by non-image forming RGCs that innervate the OPN and Tbx20 expression is essential for the development of the PLR circuitry. We discovered that Tbx20-RGCs play an important role in driving PLR but their contributions are likely masked by a more dominant driving force from other Melanopsin-expressing RGCs. Together these findings further understanding of the development and function of behaviorally relevant visual pathways.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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