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

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

Version 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.

Metrics

  • 2,873
    Page views
  • 348
    Downloads
  • 20
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Henri Leinonen
  2. Nguyen C Pham
  3. Taylor Boyd
  4. Johanes Santoso
  5. Krzysztof Palczewski
  6. Frans Vinberg
(2020)
Homeostatic plasticity in the retina is associated with maintenance of night vision during retinal degenerative disease
eLife 9:e59422.
https://doi.org/10.7554/eLife.59422

Further reading

    1. Neuroscience
    Amanda J González Segarra, Gina Pontes ... Kristin Scott
    Research Article

    Consumption of food and water is tightly regulated by the nervous system to maintain internal nutrient homeostasis. Although generally considered independently, interactions between hunger and thirst drives are important to coordinate competing needs. In Drosophila, four neurons called the interoceptive subesophageal zone neurons (ISNs) respond to intrinsic hunger and thirst signals to oppositely regulate sucrose and water ingestion. Here, we investigate the neural circuit downstream of the ISNs to examine how ingestion is regulated based on internal needs. Utilizing the recently available fly brain connectome, we find that the ISNs synapse with a novel cell-type bilateral T-shaped neuron (BiT) that projects to neuroendocrine centers. In vivo neural manipulations revealed that BiT oppositely regulates sugar and water ingestion. Neuroendocrine cells downstream of ISNs include several peptide-releasing and peptide-sensing neurons, including insulin producing cells (IPCs), crustacean cardioactive peptide (CCAP) neurons, and CCHamide-2 receptor isoform RA (CCHa2R-RA) neurons. These neurons contribute differentially to ingestion of sugar and water, with IPCs and CCAP neurons oppositely regulating sugar and water ingestion, and CCHa2R-RA neurons modulating only water ingestion. Thus, the decision to consume sugar or water occurs via regulation of a broad peptidergic network that integrates internal signals of nutritional state to generate nutrient-specific ingestion.

    1. Neuroscience
    Lucas Y Tian, Timothy L Warren ... Michael S Brainard
    Research Article

    Complex behaviors depend on the coordinated activity of neural ensembles in interconnected brain areas. The behavioral function of such coordination, often measured as co-fluctuations in neural activity across areas, is poorly understood. One hypothesis is that rapidly varying co-fluctuations may be a signature of moment-by-moment task-relevant influences of one area on another. We tested this possibility for error-corrective adaptation of birdsong, a form of motor learning which has been hypothesized to depend on the top-down influence of a higher-order area, LMAN (lateral magnocellular nucleus of the anterior nidopallium), in shaping moment-by-moment output from a primary motor area, RA (robust nucleus of the arcopallium). In paired recordings of LMAN and RA in singing birds, we discovered a neural signature of a top-down influence of LMAN on RA, quantified as an LMAN-leading co-fluctuation in activity between these areas. During learning, this co-fluctuation strengthened in a premotor temporal window linked to the specific movement, sequential context, and acoustic modification associated with learning. Moreover, transient perturbation of LMAN activity specifically within this premotor window caused rapid occlusion of pitch modifications, consistent with LMAN conveying a temporally localized motor-biasing signal. Combined, our results reveal a dynamic top-down influence of LMAN on RA that varies on the rapid timescale of individual movements and is flexibly linked to contexts associated with learning. This finding indicates that inter-area co-fluctuations can be a signature of dynamic top-down influences that support complex behavior and its adaptation.