 |
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, March 5, 2008, 28(10):2342-2352; doi:10.1523/JNEUROSCI.4784-07.2008
Previous Article | Next Article
Development/Plasticity/Repair
Genetic Control of Circuit Function: Vsx1 and Irx5 Transcription Factors Regulate Contrast Adaptation in the Mouse Retina
Daniel Kerschensteiner,1,2 Haiquan Liu,3 Chi Wa Cheng,4 Jay Demas,5 Shuk Han Cheng,4 Chi-chung Hui,6,7 Robert L. Chow,3 andRachel O. L. Wong1,2 1Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, 2Department of Biological Structure, University of Washington, Seattle, Washington 98195, 3Department of Biology, University of Victoria, Victoria, British Columbia, Canada V8W 3N5, 4Department of Biology and Chemistry, City University of Hong Kong, Kowloon, Hong Kong, China, 5Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, and 6Program in Developmental Biology, The Hospital for Sick Children, and 7Department of Molecular and Medical Genetics, University of Toronto, Toronto, Ontario, Canada M5G 1X8
Correspondence should be addressed to either of the following: Rachel O. L. Wong, Department of Biological Structure, University of Washington, Health Sciences Building, 1959 NE Pacific Street, Seattle, WA 98195, Email: wongr2{at}u.washington.edu; or Robert L. Chow, Department of Biology, University of Victoria, P.O. Box 3020, Station CSC, Victoria, British Columbia, Canada V8W 3N5, Email: bobchow{at}uvic.ca
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 linear–nonlinear model. We found that space–time 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.
Key words: contrast adaptation; retina; transcription factor; bipolar cell; retinal ganglion cell; vision
Received June 12, 2007; revised Dec. 31, 2007; accepted Jan. 4, 2008.
Correspondence should be addressed to either of the following: Rachel O. L. Wong, Department of Biological Structure, University of Washington, Health Sciences Building, 1959 NE Pacific Street, Seattle, WA 98195, Email: wongr2{at}u.washington.edu; or Robert L. Chow, Department of Biology, University of Victoria, P.O. Box 3020, Station CSC, Victoria, British Columbia, Canada V8W 3N5, Email: bobchow{at}uvic.ca
|
|
|
|
 |
|