June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Retinotopic organisation of dLGN-projecting ipRGCs in the mouse
Author Affiliations & Notes
  • Rose Richardson
    Division of Neuroscience, The University of Manchester Faculty of Biology Medicine and Health, Manchester, United Kingdom
  • Marina Gardasevic
    Division of Neuroscience, The University of Manchester Faculty of Biology Medicine and Health, Manchester, United Kingdom
  • Lucy Holmes
    Division of Neuroscience, The University of Manchester Faculty of Biology Medicine and Health, Manchester, United Kingdom
  • Jonathan Wynne
    Division of Neuroscience, The University of Manchester Faculty of Biology Medicine and Health, Manchester, United Kingdom
  • Annette Allen
    Division of Neuroscience, The University of Manchester Faculty of Biology Medicine and Health, Manchester, United Kingdom
  • Nina Milosavljevic
    Division of Neuroscience, The University of Manchester Faculty of Biology Medicine and Health, Manchester, United Kingdom
  • Robert Lucas
    Division of Neuroscience, The University of Manchester Faculty of Biology Medicine and Health, Manchester, United Kingdom
  • Footnotes
    Commercial Relationships   Rose Richardson None; Marina Gardasevic None; Lucy Holmes None; Jonathan Wynne None; Annette Allen None; Nina Milosavljevic None; Robert Lucas None
  • Footnotes
    Support  Wellcome Trust Investigator Award 210684/Z/18/Z
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 37. doi:
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      Rose Richardson, Marina Gardasevic, Lucy Holmes, Jonathan Wynne, Annette Allen, Nina Milosavljevic, Robert Lucas; Retinotopic organisation of dLGN-projecting ipRGCs in the mouse. Invest. Ophthalmol. Vis. Sci. 2023;64(8):37.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin, rendering them sensitive to light. There are at least five structurally and functionally distinct ipRGC subtypes (M1-M5), whose anatomy and physiology indicate that they differ in visual feature selectivity, that map via projections to the dorsal lateral geniculate nucleus (dLGN). To date, little is known about the relative contributions of these ipRGC subtypes to the dLGN projection. Here, we present an exploratory anatomical study defining how ipRGC subtypes map visual features to the dLGN.

Methods : Brainbow is a transgenic multicolour labelling technique that uses Cre-loxP recombination to drive stochastic expression of up to four reporter proteins in individual neurons, allowing cells to be identified by their unique profile of fluorescence. Controlled delivery of adeno-associated virus Brainbow constructs to Opn4Cre/+ mice, restricted Brainbow expression to ipRGCs. Viral vectors were injected intravitreally, transducing the inner retina to assess retinal populations and their projections to the brain, or injected into the dLGN to retrograde infect ipRGCs. We identified reporter gene expression in ipRGCs by immunohistochemistry and visualised them using confocal microscopy. Finally, we applied the computational platform-BRIAN (Brainbow Analysis of individuals Neurons) to analyse Brainbow-labelled tissue, recreating single neurons or axonal projections from densely labelled tissue with sufficient anatomical resolution for subtype quantitative classification.

Results : Using single-ipRGC tracing we showed that ipRGCs have elaborate patterns of dLGN innervation and found that several subtypes located in distinct areas of the dLGN receive direct retinal input. We identified five ipRGC subtypes involved in dLGN projections and present an overview of the topographical distribution of ipRGC subtypes in whole mounted mouse retina. The majority of ipRGCs projecting to the dLGN were classified as M4 or M5 subtypes, accounting for over 50% of projections, whilst less than 10% of dLGN-projecting ipRGCs were classified as M3.

Conclusions : This study demonstrates that ipRGC subtype diversity supports visual function and provides anatomical evidence for subtype-specific retinotopic organisation of dLGN-projecting ipRGCs to influence vision-forming behaviours.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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