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Contrast gain control and cortical TrkB signaling shape visual acuity

Nature Neuroscience volume 13, pages 642–648 (2010)Cite this article

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Abstract

During development and aging and in amblyopia, visual acuity is far below the limitations set by the retina. Expression of brain-derived neurotrophic factor (BDNF) in the visual cortex is reduced in these situations. We asked whether neurotrophic tyrosine kinase receptor, type 2 (TrkB) regulates cortical visual acuity in adult mice. We found that genetically interfering with TrkB/BDNF signaling in pyramidal cells in the mature visual cortex reduced synaptic strength and resulted in a loss of neural responses to high spatial-frequency stimuli. Responses to low spatial-frequency stimuli were unaffected. This selective loss was not accompanied by a change in receptive field sizes or plasticity, but apparent contrast was reduced. Our results indicate that a dependence on spatial frequency in the Heeger normalization model explains this selective effect of contrast reduction on high-resolution vision and suggest that it involves contrast gain control operating in the visual cortex.

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Figure 1: Expression of TrkB.T1-EGFP in pyramidal neurons of the adult visual cortex causes reduced synaptic strength.
Figure 2: Acuity is reduced in V1 of TrkB.T1-EGFP mice.
Figure 3: Apparent contrast is reduced in TrkB.T1-EGFP mice.
Figure 4: Apparent contrast reduction in TrkB.T1-EGFP mice explains acuity loss.
Figure 5: Normalization model explains the differential effect of reduced contrast on responses to high and low spatial-frequency stimuli.
Figure 6: Imaging confirms the model's prediction that population contrast tuning curves at different spatial frequencies are identical when contrast is rescaled.
Figure 7: Model predicts population spatial frequency and contrast relationships in wild-type and TrkB.T1-EGFP mice.

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Acknowledgements

We thank S. Nelson for reading the manuscript and, together with S. Van Hooser, for visual stimulation software, A. Maffei and C. de Zeeuw for discussions, R. Hartman for assistance with monocular deprivation, S. Škulj-Živkovic, S. Scheltinga and S. Riahi for genotyping and C. Pool and J. van Heerikhuize for puncta analysis macros. C.N.L., J.A.H. and J.M.H. were supported by SenterNovem BSIK grant 03053. S.C. was supported by Rotterdamse Vereniging Blindenbelangen, Algemeen Nederlandse Vereeniging ter Voorkoming van Blindheid and Stichting Blindenhulp. C.N.L. and M.H.S. were supported by a ZonMW Vidi grant.

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  1. Molecular Visual Plasticity Group, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands

    J Alexander Heimel, M Hadi Saiepour, Sridhara Chakravarthy, Josephine M Hermans & Christiaan N Levelt

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  1. J Alexander Heimel
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Contributions

C.N.L. generated the TrkB.T1-EGFP mice. J.A.H. and C.N.L. devised the experiments and wrote the manuscript. J.A.H. performed the in vivo experiments and implemented the normalization model. M.H.S. carried out the slice experiments. S.C. analyzed parvalbumin puncta. J.M.H. assisted with imaging.

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Correspondence to J Alexander Heimel.

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Heimel, J., Saiepour, M., Chakravarthy, S. et al. Contrast gain control and cortical TrkB signaling shape visual acuity. Nat Neurosci 13, 642–648 (2010). https://doi.org/10.1038/nn.2534

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