Regulation of Retinal Cone Bipolar Cell Differentiation and Photopic Vision by the CVC Homeobox Gene Vsx1

Ohtoshi, Akihira; Wang, Steven W.; Maeda, Hidetaka; Saszik, Shannon; Frishman, Laura J.; Klein, William H.; Behringer, Richard R.

doi:10.1016/j.cub.2004.02.027

Cited by 86 publications

(103 citation statements)

References 17 publications

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“…In the present study Fig. 4A shows that PDA began to alter the leading edge of the awave around 8-10 ms after the flash, consistent with other mouse studies from this lab (Maeda et al, 2003;Ohtoshi et al, 2004). In macaques effects of intravitreal PDA injection can be seen as early as 5 ms after a brief flash (Robson et al, 2003).…”

Section: Effect Of Pda On the A-wavesupporting

confidence: 90%

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Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

Shirato

Maeda

Miura

et al. 2008

Experimental Eye Research

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The purpose of this study was to determine the contributions of postreceptoral neurons to the lightadapted ERG of the Nob mouse, a model for complete-type congenital stationary night blindness (CSNB1) that lacks a b-wave from depolarizing bipolar cells. Ganzfeld ERGs were recorded from anesthetized adult control mice, control mice injected intravitreally with L-2-amino-4-phosphonobutyric acid (Control APB mice) to remove On pathway activity, and Nob mice. ERGs also were recorded after PDA (cis-2, 3-piperidine-dicarboxylic acid, 3-5 mM) was injected to block transmission to hyperpolarizing (Off) bipolar and horizontal cells, and all 3rd order neurons. Stimuli were brief (< 4 ms, 0.4 -2.5 log sc td s) and long (200 ms, 2.5 -4.6 log sc td) LED flashes (λmax = 513 nm, on a rod suppressing background (2.6 log sc td). Sinusoidal modulation of the LEDs (mean, 2.6 log sc td; contrast, 100%; 3 to 36 Hz) was used to study flicker ERGs.Brief-flash ERGs of Nob mice presented as long-lasting negative waves with a positive-going intrusion that started about 50 ms after the flash and peaked around 120 ms. Control APB mice had similar responses, and in both cases, PDA removed the positive-going intrusion. For long flashes, PDA removed a small, slow "d-wave" after light offset. With sinusoidal stimulation, the fundamental (F1) amplitude of control mice ERG peaked at 8 Hz (~70 μV). For Nob mice the peak was ~20 μV at 6 Hz before PDA and ~10 μV at 3 Hz or lower after PDA. F1 responses were present up to 21 Hz in control and Nob eyes and 15 Hz in Nob eyes after PDA. Between 3 and 6 Hz, F1 phase was 170°-210° more delayed in Nob than control mice; phase was hardly altered by PDA. With vector analysis, a substantial postreceptoral input to the Nob flicker ERG was revealed. In control mice, the second harmonic (F2) response showed peaks of ~10 μV at 3 Hz and 13 Hz. Nob mice showed almost no F2. In summary, in this study it was found that in Nob mice, postreceptoral neurons from the Off pathway make a positive-going contribution to the light-adapted flash ERG, and contribute substantially to sinusoidal flicker ERG.

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Section: Effect Of Pda On the A-wavesupporting

confidence: 90%

“…As previously described for primates, as well as for mice, Off pathway activity contributes to the leading edge of the a-wave under light-adapted conditions quite early in the response (Bush and Sieving, 1994;Robson et al, 2003;Maeda et al, 2003;Ohtoshi et al, 2004;Sharma et al, 2005). In the present study Fig.…”

Section: Effect Of Pda On the A-wavesupporting

confidence: 83%

Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

Shirato

Maeda

Miura

et al. 2008

Experimental Eye Research

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“…Previous work showed overlapping defects in the expression of cell-specific markers in OFF but not ON cone bipolar cells of mice lacking either Vsx1 or Irx5 (Chow et al, 2004;Ohtoshi et al, 2004;Cheng et al, 2005). In addition, OFF but not ON RGCs recorded from Vsx1 Ϫ/Ϫ mice fired on average fewer action potentials in response to diffuse luminance steps compared with wild-type counterparts (Chow et al, 2004).…”

Section: Light Response Properties Of Rgcs In Control and Dko Micementioning

confidence: 86%

“…First, we identified several functional RGC types in mice, analyzed their space-time receptive fields, response threshold, gain, and range, and determined how these parameters change during adaptation to temporal contrast. We then used these parameters to ask whether specific aspects of retinal network function are under selective genetic control of the transcription factors Vsx1 and Irx5, which regulate expression profiles of OFF cone bipolar cells (Chow et al, 2004;Ohtoshi et al, 2004;Cheng et al, 2005). We found that space-time receptive fields are indistinguishable between genotypes and that differences in response threshold, gain, or range in retinas from dko compared with control mice are cell type specific and restricted to the OFF but not the ON pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Deletion of either gene did not affect the number or gross morphology of bipolar cells but led to distinct changes in the expression profile of the several OFF cone bipolar cell types (Chow et al, 2004;Cheng et al, 2005). In addition, ERGs of Vsx1-deficient mice showed a reduced b-wave, a measure of bipolar cell activity, and OFF but not ON RGCs fired on average fewer spikes in response to steps in light intensity compared with their wild-type counterparts (Chow et al, 2004;Ohtoshi et al, 2004). In contrast, preliminary studies revealed no specific b-wave defects in ERGs from Irx5-deficient mice (Cheng et al, 2005).…”

Section: Introductionmentioning

confidence: 96%

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Genetic Control of Circuit Function:Vsx1andIrx5Transcription Factors Regulate Contrast Adaptation in the Mouse Retina

Kerschensteiner¹,

Liu²,

Cheng³

et al. 2008

J. Neurosci.

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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 Irx5Ϫ/Ϫ 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 Irx5Ϫ/Ϫ 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 Irx5Ϫ/Ϫ 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.

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Elucidating the Molecular Genetic Basis of the Corneal Dystrophies

Aldave¹

2007

Arch Ophthalmol

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Regulation of Retinal Cone Bipolar Cell Differentiation and Photopic Vision by the CVC Homeobox Gene Vsx1

Cited by 86 publications

References 17 publications

Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

Postreceptoral contributions to the light-adapted ERG of mice lacking b-waves

Genetic Control of Circuit Function:Vsx1andIrx5Transcription Factors Regulate Contrast Adaptation in the Mouse Retina

Elucidating the Molecular Genetic Basis of the Corneal Dystrophies

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