1. Neuroscience
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Homeostatic plasticity in the retina is associated with maintenance of night vision during retinal degenerative disease

  1. Henri Leinonen  Is a corresponding author
  2. Nguyen C Pham
  3. Taylor Boyd
  4. Johanes Santoso
  5. Krzysztof Palczewski
  6. Frans Vinberg  Is a corresponding author
  1. University of California, Irvine, United States
  2. University of Utah, United States
Research Article
  • Cited 4
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Cite this article as: eLife 2020;9:e59422 doi: 10.7554/eLife.59422

Abstract

Neuronal plasticity of the inner retina has been observed in response to photoreceptor degeneration. Typically, this phenomenon has been considered maladaptive and may preclude vision restoration in the blind. However, several recent studies utilizing triggered photoreceptor ablation have shown adaptive responses in bipolar cells expected to support normal vision. Whether such homeostatic plasticity occurs during progressive photoreceptor degenerative disease to help maintain normal visual behavior is unknown. We addressed this issue in an established mouse model of Retinitis Pigmentosa caused by the P23H mutation in rhodopsin. We show robust modulation of the retinal transcriptomic network, reminiscent of the neurodevelopmental state, and potentiation of rod – rod bipolar cell signaling following rod photoreceptor degeneration. Additionally, we found highly sensitive night vision in P23H mice even when more than half of the rod photoreceptors were lost. These results suggest retinal adaptation leading to persistent visual function during photoreceptor degenerative disease.

Data availability

Sequencing data have been uploaded in GEO, accession numbers: GSE152474 (1-month-old samples) and GSE156533 (3-month-old samples).

The following data sets were generated

Article and author information

Author details

  1. Henri Leinonen

    Gavin Herbert Eye Institute, Ophthalmology, University of California, Irvine, Irvine, United States
    For correspondence
    hleinone@uci.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0388-832X
  2. Nguyen C Pham

    Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Taylor Boyd

    Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Johanes Santoso

    Gavin Herbert Eye Institute, Ophthalmology, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Krzysztof Palczewski

    1.Gavin Herbert Eye Institute, Department of Ophthalmology, University of California, Irvine, Irvine, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0788-545X
  6. Frans Vinberg

    Ophthalmology & Visual Sciences, University of Utah, Salt Lake City, United States
    For correspondence
    frans.vinberg@utah.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3439-4979

Funding

National Eye Institute (R00 EY026651)

  • Frans Vinberg

Research to Prevent Blindness (Unrestricted grant to the Department of Ophthalmology and Visual Sciences,University of Utah)

  • Frans Vinberg

International Retinal Research Foundation (Regular Grant)

  • Frans Vinberg

Research to Prevent Blindness (Dr. H. James and Carole Free Career Development)

  • Frans Vinberg

National Eye Institute (R01 EY009339)

  • Krzysztof Palczewski

National Eye Institute (R24 EY027283)

  • Krzysztof Palczewski

Eye and Tissue Bank Foundation (Postdoctoral Award)

  • Henri Leinonen

Finnish Cultural Foundation (Postdoctoral Award)

  • Henri Leinonen

Orion Research Foundation (Postdoctoral Award)

  • Henri Leinonen

Research to Prevent Blindness (Unrestricted grant to the Department of Ophthalmology,University of California,Irvine)

  • Krzysztof Palczewski

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experimental protocols adhered to Guide for the Care and Use of Laboratory Animals and were approved by the institutional Animal Studies Committees at the University of Utah (protocol #20-17015) and University of California, Irvine (protocol #AUP-18-124).

Reviewing Editor

  1. Lois Smith, Boston Children's Hospital/Harvard Medical School, United States

Publication history

  1. Received: May 28, 2020
  2. Accepted: September 8, 2020
  3. Accepted Manuscript published: September 22, 2020 (version 1)
  4. Version of Record published: October 1, 2020 (version 2)

Copyright

© 2020, Leinonen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

    1. Neuroscience
    P Christiaan Klink et al.
    Research Article Updated

    Population receptive field (pRF) modeling is a popular fMRI method to map the retinotopic organization of the human brain. While fMRI-based pRF maps are qualitatively similar to invasively recorded single-cell receptive fields in animals, it remains unclear what neuronal signal they represent. We addressed this question in awake nonhuman primates comparing whole-brain fMRI and large-scale neurophysiological recordings in areas V1 and V4 of the visual cortex. We examined the fits of several pRF models based on the fMRI blood-oxygen-level-dependent (BOLD) signal, multi-unit spiking activity (MUA), and local field potential (LFP) power in different frequency bands. We found that pRFs derived from BOLD-fMRI were most similar to MUA-pRFs in V1 and V4, while pRFs based on LFP gamma power also gave a good approximation. fMRI-based pRFs thus reliably reflect neuronal receptive field properties in the primate brain. In addition to our results in V1 and V4, the whole-brain fMRI measurements revealed retinotopic tuning in many other cortical and subcortical areas with a consistent increase in pRF size with increasing eccentricity, as well as a retinotopically specific deactivation of default mode network nodes similar to previous observations in humans.

    1. Developmental Biology
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    The transcription factor activating protein two gamma (AP2γ) is an important regulator of neurogenesis both during embryonic development as well as in the postnatal brain, but its role for neurophysiology and behavior at distinct postnatal periods is still unclear. In this work, we explored the neurogenic, behavioral, and functional impact of a constitutive and heterozygous AP2γ deletion in mice from early postnatal development until adulthood. AP2γ deficiency promotes downregulation of hippocampal glutamatergic neurogenesis, altering the ontogeny of emotional and memory behaviors associated with hippocampus formation. The impairments induced by AP2γ constitutive deletion since early development leads to an anxious-like phenotype and memory impairments as early as the juvenile phase. These behavioral impairments either persist from the juvenile phase to adulthood or emerge in adult mice with deficits in behavioral flexibility and object location recognition. Collectively, we observed a progressive and cumulative impact of constitutive AP2γ deficiency on the hippocampal glutamatergic neurogenic process, as well as alterations on limbic-cortical connectivity, together with functional behavioral impairments. The results herein presented demonstrate the modulatory role exerted by the AP2γ transcription factor and the relevance of hippocampal neurogenesis in the development of emotional states and memory processes.