Genetic Control of Circuit Function: Vsx1 and Irx5 Transcription Factors Regulate Contrast Adaptation in the Mouse Retina

Kerschensteiner, D., Liu, H., Cheng, C. W., Demas, J., Cheng, S. H., Hui, C. c., Chow, R. L., Wong, R. O. L. (March 2008) Genetic Control of Circuit Function: Vsx1 and Irx5 Transcription Factors Regulate Contrast Adaptation in the Mouse Retina. J. Neurosci., 28 (10). pp. 2342-2352.

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Abstract

Transcriptional programs guide the specification of neural cell types in the developing nervous system. However, it is unclear whether such programs also control specific aspects of neural circuit function at maturity. In the mammalian retina, Vsx1 and Irx5 transcription factors are present in a subset of bipolar interneurons that convey signals from photoreceptors to ganglion cells. The biased expression of Vsx1 and Irx5 in hyperpolarizing OFF compared with depolarizing ON bipolar cells suggests that these transcription factors may selectively regulate signal processing in OFF circuits. To test this hypothesis, we generated mice lacking both Vsx1 and Irx5. Bipolar cells in these mice were morphologically normal, but the expression of cell-specific markers in some OFF but not ON bipolar cells was reduced or absent. To assess visual function in Vsx1/Irx5/ retinas, we recorded light responses from ensembles of retinal ganglion cells (RGCs). We first identified functional RGC types in control mice and describe their response properties and adaptation to temporal contrast using a simple linearnonlinear model. We found that spacetime receptive fields of RGCs are unchanged in Vsx1/Irx5/ mice compared with control retinas. In contrast, response threshold, gain, and range were lowered in a cell-type-specific manner in OFF but not ON RGCs in Vsx1/Irx5/ retinas. Finally, we discovered that the ability to adapt to temporal contrast is greatly reduced in OFF RGCs in the double mutant, suggesting that Vsx1 and Irx5 control specific aspects of visual function in circuits of the mammalian retina.

Item Type:	Paper
Uncontrolled Keywords:	contrast adaptation retina transcription factor bipolar cell retinal ganglion cell vision
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification organism description > animal organism description > animal > mammal > rodent > mouse organs, tissues, organelles, cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types organs, tissues, organelles, cell types and functions > tissues types and functions > retina organs, tissues, organelles, cell types and functions > tissues types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Demas, Jay
Communities:	CSHL labs > Cline lab
Depositing User:	Matt Covey
Date:	5 March 2008
Date Deposited:	26 Feb 2013 20:57
Last Modified:	27 Dec 2023 14:41
PMCID:	PMC6671180
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/27533

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