Contribution of human melanopsin retinal ganglion cells to steady-state pupil responses

The recent discovery of melanopsin-containing retinal ganglion cells (mRGCs) has led to a fundamental reassessment of non-image forming processing, such as circadian photoentrainment and the pupillary light reflex. In the conventional view of retinal physiology, rods and cones were assumed to be the only photoreceptors in the eye and were, therefore, considered responsible for non-image processing. However, signals from mRGCs contribute to this non-image forming processing along with cone-mediated luminance signals; although both signals contribute, it is unclear how these signals are summed. We designed and built a novel multi-primary stimulation system to stimulate mRGCs independently of other photoreceptors using a silent-substitution technique within a bright steady background. The system allows direct measurements of pupillary functions for mRGCs and cones. We observed a significant change in steady-state pupil diameter when we varied the excitation of mRGC alone, with no change in luminance and colour. Furthermore, the change in pupil diameter induced by mRGCs was larger than that induced by a variation in luminance alone: that is, for a bright steady background, the mRGC signals contribute to the pupillary pathway by a factor of three times more than the L- and M-cone signals.

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Relation of Brightness to Threshold for Light-Adapted and Dark-Adapted Rods and Cones: Effects of Retinal Eccentricity and Target Size

Perception ◽

10.1068/p090633 ◽

1980 ◽

Vol 9 (6) ◽

pp. 633-650 ◽

Cited By ~ 4

Author(s):

Bruce Drum

Keyword(s):

Retinal Ganglion Cells ◽

Channel Model ◽

Ganglion Cells ◽

The Other ◽

Target Size ◽

Retinal Eccentricity ◽

Retinal Ganglion ◽

Threshold Functions ◽

Rods And Cones ◽

Matching Procedure

‘Equal-brightness' functions of retinal eccentricity and target diameter were measured by a matching procedure, and compared with the corresponding threshold functions for four different adaptation conditions: light-adapted cones (LAC), dark-adapted cones (DAC), light-adapted rods (LAR) and dark-adapted rods (DAR). The separation between log brightness matches and log thresholds decreased with eccentricity and increased with target size for all adaptation conditions, but overall separation was substantially greater for the DAR condition than for the other three. A two-channel model of achromatic brightness is proposed to explain the results. The model assumes ‘strong’ and ‘weak’ channels, which contribute unequally to brightness. These channels are tentatively identified with tonic and phasic classes of retinal ganglion cells.

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Transient and steady state stimulus-response relations for cat retinal ganglion cells

Vision Research ◽

10.1016/0042-6989(70)90003-9 ◽

1970 ◽

Vol 10 (6) ◽

pp. 461-477 ◽

Cited By ~ 22

Author(s):

R.W. Winters ◽

J.W. Walters

Keyword(s):

Steady State ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Retinal Ganglion ◽

Stimulus Response ◽

Transient And Steady State

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Functional diversity of human intrinsically photosensitive retinal ganglion cells

Science ◽

10.1126/science.aaz0898 ◽

2019 ◽

Vol 366 (6470) ◽

pp. 1251-1255 ◽

Cited By ~ 10

Author(s):

Ludovic S. Mure ◽

Frans Vinberg ◽

Anne Hanneken ◽

Satchidananda Panda

Keyword(s):

Retinal Ganglion Cells ◽

Preparation Method ◽

Ganglion Cells ◽

Organ Donor ◽

Retinal Ganglion ◽

Visual Responses ◽

Human Organ ◽

Rods And Cones ◽

Light Signals ◽

Human And Mouse

Intrinsically photosensitive retinal ganglion cells (ipRGCs) are a subset of cells that participate in image-forming and non–image-forming visual responses. Although both functional and morphological subtypes of ipRGCs have been described in rodents, parallel functional subtypes have not been identified in primate or human retinas. In this study, we used a human organ donor preparation method to measure human ipRGCs’ photoresponses. We discovered three functional ipRGC subtypes with distinct sensitivities and responses to light. The response of one ipRGC subtype appeared to depend on exogenous chromophore supply, and this response is conserved in both human and mouse retinas. Rods and cones also provided input to ipRGCs; however, each subtype integrated outer retina light signals in a distinct fashion.

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Intrinsically Photosensitive Retinal Ganglion Cells of the Human Retina

Frontiers in Neurology ◽

10.3389/fneur.2021.636330 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ludovic S. Mure

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Life Quality ◽

Well Being ◽

Therapeutic Interventions ◽

Diagnostic Tools ◽

Human Retina ◽

Retinal Ganglion ◽

Rods And Cones ◽

Light And Gene Expression

Light profoundly affects our mental and physical health. In particular, light, when not delivered at the appropriate time, may have detrimental effects. In mammals, light is perceived not only by rods and cones but also by a subset of retinal ganglion cells that express the photopigment melanopsin that renders them intrinsically photosensitive (ipRGCs). ipRGCs participate in contrast detection and play critical roles in non-image-forming vision, a set of light responses that include circadian entrainment, pupillary light reflex (PLR), and the modulation of sleep/alertness, and mood. ipRGCs are also found in the human retina, and their response to light has been characterized indirectly through the suppression of nocturnal melatonin and PLR. However, until recently, human ipRGCs had rarely been investigated directly. This gap is progressively being filled as, over the last years, an increasing number of studies provided descriptions of their morphology, responses to light, and gene expression. Here, I review the progress in our knowledge of human ipRGCs, in particular, the different morphological and functional subtypes described so far and how they match the murine subtypes. I also highlight questions that remain to be addressed. Investigating ipRGCs is critical as these few cells play a major role in our well-being. Additionally, as ipRGCs display increased vulnerability or resilience to certain disorders compared to conventional RGCs, a deeper knowledge of their function could help identify therapeutic approaches or develop diagnostic tools. Overall, a better understanding of how light is perceived by the human eye will help deliver precise light usage recommendations and implement light-based therapeutic interventions to improve cognitive performance, mood, and life quality.

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Intrinsically Photosensitive Retinal Ganglion Cells

Physiological Reviews ◽

10.1152/physrev.00013.2010 ◽

2010 ◽

Vol 90 (4) ◽

pp. 1547-1581 ◽

Cited By ~ 210

Author(s):

Michael Tri Hoang Do ◽

King-Wai Yau

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Small Population ◽

Retinal Ganglion ◽

Visual Functions ◽

Rods And Cones ◽

Living Things ◽

Rotation Of The Earth ◽

Life On Earth ◽

And Behavior

Life on earth is subject to alternating cycles of day and night imposed by the rotation of the earth. Consequently, living things have evolved photodetective systems to synchronize their physiology and behavior with the external light-dark cycle. This form of photodetection is unlike the familiar “image vision,” in that the basic information is light or darkness over time, independent of spatial patterns. “Nonimage” vision is probably far more ancient than image vision and is widespread in living species. For mammals, it has long been assumed that the photoreceptors for nonimage vision are also the textbook rods and cones. However, recent years have witnessed the discovery of a small population of retinal ganglion cells in the mammalian eye that express a unique visual pigment called melanopsin. These ganglion cells are intrinsically photosensitive and drive a variety of nonimage visual functions. In addition to being photoreceptors themselves, they also constitute the major conduit for rod and cone signals to the brain for nonimage visual functions such as circadian photoentrainment and the pupillary light reflex. Here we review what is known about these novel mammalian photoreceptors.

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Retinal ganglion cells: a functional interpretation of dendritic morphology

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1982.0084 ◽

1982 ◽

Vol 298 (1090) ◽

pp. 227-263 ◽

Cited By ~ 261

Keyword(s):

Steady State ◽

Electrical Properties ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Dendritic Tree ◽

Input Resistance ◽

Excitatory Input ◽

Resting Potential ◽

Retinal Ganglion ◽

Strongly Nonlinear

The electrical properties of the different anatomical types of retinal ganglion cells in the cat were calculated on the basis of passive cable theory from measurements made on histological material. Standard values for the electrical parameters were assumed (R 1 = 70 Ω cm, C m = 2 μF cm -2 , R m = 2500 Ω cm 2 ). We conclude that these neurons need not be equipotential despite their small dimensions, mainly because of their extensive branching. The interactions between excitation and inhibition when the inhibitory battery is near the resting potential can be strongly nonlinear in these cells. To characterize the different types of ganglion cells in terms of this property we introduce the factor by which the soma depolarization induced by a given excitatory input is reduced by inhibition. In this framework we analyse some of the integrative properties of an arbitrary passive dendritic tree and we then derive the functional properties that are characteristic for the various types of ganglion cells. Our main results are: (i) Nonlinear saturation at the synapses may be made effectively smaller by spreading the same (conductance) input among several subunits on the dendritic field. Subunits are defined as regions of the dendritic field that are somewhat isolated from each other and roughly equipotential within. (ii) Shunting inhibition can specifically veto an excitatory input, if it is located on the direct path to the soma. The F values can then be very high even when the excitatory inputs are much larger than the inhibitory, as long as the absolute value of inhibition is not too small. Inhibition more distal than excitation is much less effective. (iii) Specific branching patterns coupled with suitable distribution of synapses are potentially able to support complex information processing operations on the incoming excitatory and inhibitory signals. The quantitative analysis of the morphology of cat retinal ganglion cells leads to the following specific conclusions: (i) None of the cells examined satisfies Rail’s equivalent cylinder condition. The dendritic tree cannot be satisfactorily approximated by a non-tapering cylinder. (ii) Under the assumption of a passive membrane, the dendritic architecture of the different types of retinal ganglion cells reflects characteristically different electrical properties, which are likely to be relevant for their physiological function and their information processing role: ( a ) α cells have spatially inhomogeneous electrical properties, with many subunits. Within each subunit nonlinear effects may take place; between subunits good linear summation is expected. F values are relatively low. ( b ) β cells at small eccentricities have rather homogeneous electrical properties. Even distal inputs are weighted rather uniformly. Electrical inhomogeneities of the a type appear for P cells at larger eccentricities. F values are low. ( c ) γ-like cells have few subunits, each with high input resistance underlying nonlinear saturation effects possibly related to a sluggish character. F values are high: inhibition of the shunting type can interact in a strongly nonlinear way with excitatory conductance inputs. ( d ) δ-like cells show many subunits with a high input resistance, covering well the dendritic area. Within each subunit inhibition on the direct path to the soma can specifically veto a more distal excitation. It is conjectured that such a synaptic organization superimposed on the δ cell morphology underlies directional selectivity to motion. (iii) Most of our data refer to steady-state properties. They probably apply, however, to all light evoked signals, since transient inputs with time to peak of 30 ms or more can be treated in terms of steady-state properties of the ganglion cells studied. (iv) All our results are affected only slightly by varying the parameter values within reasonable ranges. If, however, the membrane resistance were very high, all ganglion cells would approach equipotentiality. For R m = 8000 Ω cm 2 subunits essentially disappear in all types of ganglion cells (for steady state inputs). Our results concerning nonlinear interaction of excitation and inhibition ( values) would, however, remain valid even for much larger values of R m and for any value of R 1 larger than 30-50 Ω cm. The critical requirement is that peak inhibitory conductance changes must be sufficiently large (around 5 x 10 -8 S) with an equilibrium potential close to the resting potential. Underestimation of the diameters of the dendritic branches may affect these conclusions ( F could be significantly lower).

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