A subset of ipRGCs regulates both maturation of the circadian clock and segregation of retinogeniculate projections in mice
- Johns Hopkins University, United States
- University of Akron, United States
- National Institute of Mental Health, National Institute of Health, United States
- Brown University, United States
- Washington University, United States
- Insistut de Recherches Cliniques de Montréal, Canada
Abstract
The visual system consists of two major subsystems, image-forming circuits that drive conscious vision and non-image-forming circuits for behaviors such as circadian photoentrainment. While historically considered non-overlapping, recent evidence has uncovered crosstalk between these subsystems. Here we investigated shared developmental mechanisms. We revealed an unprecedented role for light in the maturation of the circadian clock and discovered that intrinsically photosensitive retinal ganglion cells (ipRGCs) are critical for this refinement process. In addition, ipRGCs regulate retinal waves independent of light, and developmental ablation of a subset of ipRGCs disrupts eye-specific segregation of retinogeniculate projections. Specifically, a subset of ipRGCs, comprising ~200 cells and which project intraretinally and to circadian centers in the brain, are sufficient to mediate both of these developmental processes. Thus, this subset of ipRGCs constitute a shared node in the neural networks that mediate light-dependent maturation of the circadian clock and light-independent refinement of retinogeniculate projections.
Article and author information
Author details
William Thomas Keenan
Funding
National Institute of General Medical Sciences (GM076430)
- Samer Hattar
National Eye Institute (F32-EY20108)
- Jordan M Renna
National Eye Institute (R15EY026255)
- Jordan M Renna
Canadian Institutes of Health Research (MOP-77570)
- Michel Cayouette
National Eye Institute (R01-EY019053)
- Samer Hattar
David and Lucile Packard Foundation
- Samer Hattar
Alfred P. Sloan Foundation
- Samer Hattar
Johns Hopkins University
- Samer Hattar
National Eye Institute (R01-EY017137)
- David M Berson
National Institute on Deafness and Other Communication Disorders (DC007395)
- Haiqing Zhao
National Institute of General Medical Sciences (R01-GM104991)
- Erik D Herzog
National Heart, Lung, and Blood Institute (R01-HL089742)
- Paul A Gray
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animals were housed and treated in accordance with NIH and IACUC guidelines, and used protocols approved by the Johns Hopkins University and Brown University Animal Care and Use Committees (Protocol numbers MO16A212 and 1010040).
Copyright
© 2017, Chew 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
-
- 3,692
- views
-
- 753
- downloads
-
- 70
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
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)
A subset of ipRGCs regulates both maturation of the circadian clock and segregation of retinogeniculate projections in mice
eLife 6:e22861.
https://doi.org/10.7554/eLife.22861
Further reading
-
- Computational and Systems Biology
- Neuroscience
Diffusional kurtosis imaging (DKI) is a methodology for measuring the extent of non-Gaussian diffusion in biological tissue, which has shown great promise in clinical diagnosis, treatment planning, and monitoring of many neurological diseases and disorders. However, robust, fast, and accurate estimation of kurtosis from clinically feasible data acquisitions remains a challenge. In this study, we first outline a new accurate approach of estimating mean kurtosis via the sub-diffusion mathematical framework. Crucially, this extension of the conventional DKI overcomes the limitation on the maximum b-value of the latter. Kurtosis and diffusivity can now be simply computed as functions of the sub-diffusion model parameters. Second, we propose a new fast and robust fitting procedure to estimate the sub-diffusion model parameters using two diffusion times without increasing acquisition time as for the conventional DKI. Third, our sub-diffusion-based kurtosis mapping method is evaluated using both simulations and the Connectome 1.0 human brain data. Exquisite tissue contrast is achieved even when the diffusion encoded data is collected in only minutes. In summary, our findings suggest robust, fast, and accurate estimation of mean kurtosis can be realised within a clinically feasible diffusion-weighted magnetic resonance imaging data acquisition time.
-
- Neuroscience
The retina transforms patterns of light into visual feature representations supporting behaviour. These representations are distributed across various types of retinal ganglion cells (RGCs), whose spatial and temporal tuning properties have been studied extensively in many model organisms, including the mouse. However, it has been difficult to link the potentially nonlinear retinal transformations of natural visual inputs to specific ethological purposes. Here, we discover a nonlinear selectivity to chromatic contrast in an RGC type that allows the detection of changes in visual context. We trained a convolutional neural network (CNN) model on large-scale functional recordings of RGC responses to natural mouse movies, and then used this model to search in silico for stimuli that maximally excite distinct types of RGCs. This procedure predicted centre colour opponency in transient suppressed-by-contrast (tSbC) RGCs, a cell type whose function is being debated. We confirmed experimentally that these cells indeed responded very selectively to Green-OFF, UV-ON contrasts. This type of chromatic contrast was characteristic of transitions from ground to sky in the visual scene, as might be elicited by head or eye movements across the horizon. Because tSbC cells performed best among all RGC types at reliably detecting these transitions, we suggest a role for this RGC type in providing contextual information (i.e. sky or ground) necessary for the selection of appropriate behavioural responses to other stimuli, such as looming objects. Our work showcases how a combination of experiments with natural stimuli and computational modelling allows discovering novel types of stimulus selectivity and identifying their potential ethological relevance.
