scholarly journals Dopamine D1 and D4 receptors contribute to light adaptation in ON-sustained retinal ganglion cells

2021 ◽  
Author(s):  
Michael Daniel Flood ◽  
Erika D Eggers
Keyword(s):  
Light Adaptation ◽  
Dynamic Range ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Cell Responses ◽  
Light Levels ◽  
Excitatory Activity ◽  
Effect Of Light

The adaptation of ganglion cells to increasing light levels is a crucial property of the retina. The retina must respond to light intensities that vary by 10-12 orders of magnitude, but the dynamic range of ganglion cell responses covers only ~3 orders of magnitude. Dopamine is a crucial neuromodulator for light adaptation and activates receptors in the D1 and D2 families. D1Rs are expressed on horizontal cells and some bipolar, amacrine and ganglion cells. In the D2 family D2Rs are expressed on dopaminergic amacrine cells and D4Rs are primarily expressed on photoreceptors. However, the roles of activating these receptors to modulate the synaptic properties of the inputs to ganglion cells are not yet clear. Here we used single cell retinal patch-clamp recordings from the mouse retina to determine how activating D1Rs and D4Rs changed the light-evoked and spontaneous excitatory inputs to ON-sustained (ON-s) ganglion cells. We found that both D1R and D4R activation decrease the light-evoked excitatory inputs to ON-s ganglion cells, but that only the sum of the peak response decrease due to activating the two receptors was similar to the effect of light adaptation to a rod-saturating background. The largest effects on spontaneous excitatory activity of both D1R and D4R agonists was on the frequency of events, suggesting that both D1Rs and D4Rs are acting upstream of the ganglion cells.

scholarly journals Dopamine D1 and D4 receptors contribute to light adaptation in ON-sustained retinal ganglion cells

2020 ◽  
Author(s):  
Michael D. Flood ◽  
Erika D. Eggers
Keyword(s):  
Light Adaptation ◽  
Dynamic Range ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Cell Responses ◽  
Light Levels ◽  
Excitatory Activity ◽  
Effect Of Light

AbstractAdaptation of ganglion cells to increasing light levels is a crucial property of the retina. The retina must respond to light intensities that vary by 10-12 orders of magnitude, but the dynamic range of ganglion cell responses only covers ~1000 orders of magnitude. Dopamine is a crucial neuromodulator for light adaptation and activates receptors in the D1 family – D1Rs that are expressed on horizontal cells and some bipolar and ganglion cells- and the D2 family – D2Rs that are expressed on dopaminergic amacrine cells and D4Rs that are primarily expressed on photoreceptors. However, how these receptors change the synaptic properties of the inputs to ganglion cells is not yet clear. Here we used single cell retinal patch-clamp recordings from the mouse retina to determine how activating D1Rs and D4Rs changed the light-evoked and spontaneous excitatory inputs to ON-sustained (ON-s) ganglion cells. We found that both D1R and D4R activation decrease the light-evoked excitatory inputs to ON-s ganglion cells, but that only the sum of activating the two receptors was similar to the effect of light adaptation to a rod-saturating background. The largest effects on spontaneous excitatory activity of both D1R and D4R agonists was on the frequency of events, suggesting that D1Rs and D4Rs are acting upstream of the ganglion cells.

Light adaptation in the primate retina: Analysis of changes in gain and dynamics of monkey retinal ganglion cells

1990 ◽  
Vol 4 (1) ◽  
pp. 75-93 ◽  
Author(s):  
Keith Purpura ◽  
Daniel Tranchina ◽  
Ehud Kaplan ◽  
Robert M. Shapley
Keyword(s):  
Retinal Ganglion Cells ◽  
Negative Feedback ◽  
Light Adaptation ◽  
Ganglion Cells ◽  
Human Subjects ◽  
Light Level ◽  
Retinal Ganglion ◽  
M Cell ◽  
Feedback Model ◽  
Light Levels

AbstractThe responses of monkey retinal ganglion cells to sinusoidal stimuli of various temporal frequencies were measured and analyzed at a number of mean light levels. Temporal modulation tuning functions (TMTFs) were measured at each mean level by varying the drift rate of a sine-wave grating of fixed spatial frequency and contrast. The changes seen in ganglion cell temporal responses with changes in adaptation state were similar to those observed in human subjects and in turtle horizontal cells and cones tested with sinusoidally flickering stimuli; “Weber's Law” behavior was seen at low temporal frequencies but not at higher temporal frequencies. Temporal responses were analyzed in two ways: (1) at each light level, the TMTFs were fit by a model consisting of a cascade of low- and high-pass filters; (2) the family of TMTFs collected over a range of light levels for a given cell was fit by a linear negative feedback model in which the gain of the feedback was proportional to the mean light level. Analysis (1) revealed that the temporal responses of one class of monkey ganglion cells (M cells) were more phasic at both photopic and mesopic light levels than the responses of P ganglion cells. In analysis (2), the linear negative feedback model accounted reasonably well for changes in gain and dynamics seen in three P cells and one M cell. From the feedback model, it was possible to estimate the light level at which the dark-adapted gain of the cone pathways in the primate retina fell by a factor of two. This value was two to three orders of magnitude lower than the value estimated from recordings of isolated monkey cones. Thus, while a model which includes a single stage of negative feedback can account for the changes in gain and dynamics associated with light adaptation in the photopic and mesopic ranges of vision, the underlying physical mechanisms are unknown and may involve elements in the primate retina other than the cone.

scholarly journals PTEN Expression Regulates Gap Junction Connectivity in the Retina

2021 ◽  
Vol 15 ◽  
Author(s):  
Ashley M. Chen ◽  
Shaghauyegh S. Azar ◽  
Alexander Harris ◽  
Nicholas C. Brecha ◽  
Luis Pérez de Sevilla Müller
Keyword(s):  
Gap Junction ◽  
Retinal Ganglion Cells ◽  
Vision Loss ◽  
Ganglion Cells ◽  
Dendritic Structure ◽  
Amacrine Cells ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Cell Coupling ◽  
Cell Degeneration

Manipulation of the phosphatase and tensin homolog (PTEN) pathway has been suggested as a therapeutic approach to treat or prevent vision loss due to retinal disease. In this study, we investigated the effects of deleting one copy of Pten in a well-characterized class of retinal ganglion cells called α-ganglion cells in the mouse retina. In Pten+/– retinas, α-ganglion cells did not exhibit major changes in their dendritic structure, although most cells developed a few, unusual loop-forming dendrites. By contrast, α-ganglion cells exhibited a significant decrease in heterologous and homologous gap junction mediated cell coupling with other retinal ganglion and amacrine cells. Additionally, the majority of OFF α-ganglion cells (12/18 cells) formed novel coupling to displaced amacrine cells. The number of connexin36 puncta, the predominant connexin that mediates gap junction communication at electrical synapses, was decreased by at least 50% on OFF α-ganglion cells. Reduced and incorrect gap junction connectivity of α-ganglion cells will affect their functional properties and alter visual image processing in the retina. The anomalous connectivity of retinal ganglion cells would potentially limit future therapeutic approaches involving manipulation of the Pten pathway for treating ganglion cell degeneration in diseases like glaucoma, traumatic brain injury, Parkinson’s, and Alzheimer’s diseases.

scholarly journals Evidence for novel transient clusters of cholinergic ganglion cells in the neonatal mouse retina

2019 ◽  
Author(s):  
Jean de Montigny ◽  
Vidhyasankar Krishnamoorthy ◽  
Fernando Rozenblit ◽  
Tim Gollisch ◽  
Evelyne Sernagor
Keyword(s):  
Ganglion Cells ◽  
Amacrine Cells ◽  
Bipolar Cells ◽  
Neonatal Mouse ◽  
Mouse Retina ◽  
Retinal Ganglion ◽  
Electrical Imaging ◽  
Subplate Neurons ◽  
Starburst Amacrine Cells ◽  
Cholinergic Cell

AbstractWaves of spontaneous activity sweep across the neonatal mouse retinal ganglion cell (RGC) layer, driven by directly interconnected cholinergic starburst amacrine cells (the only known retinal cholinergic cells) from postnatal day (P) 0-10, followed by waves driven by glutamatergic bipolar cells. We found transient clusters of cholinergic RGC-like cells around the optic disc during the period of cholinergic waves. They migrate towards the periphery between P2-9 and then they disappear. Pan-retinal multielectrode array recordings reveal that cholinergic wave origins follow a similar developmental center-to-periphery pattern. Electrical imaging unmasks hotspots of dipole electrical activity occurring in the vicinity of wave origins. We propose that these activity hotspots are sites for wave initiation and are related to the cholinergic cell clusters, reminiscent of activity in transient subplate neurons in the developing cortex, suggesting a universal hyper-excitability mechanism in developing CNS networks during the critical period for brain wiring.

scholarly journals Defocused Images Change Multineuronal Firing Patterns in the Mouse Retina

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 530 ◽  
Author(s):  
Seema Banerjee ◽  
Qin Wang ◽  
Chung Him So ◽  
Feng Pan
Keyword(s):  
Edge Detection ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Public Health Problem ◽  
Amacrine Cells ◽  
The United States ◽  
Mouse Retina ◽  
Major Public Health Problem ◽  
Retinal Ganglion ◽  
Firing Patterns

Myopia is a major public health problem, affecting one third of the population over 12 years old in the United States and more than 80% of people in Hong Kong. Myopia is attributable to elongation of the eyeball in response to defocused images that alter eye growth and refraction. It is known that the retina can sense the focus of an image, but the effects of defocused images on signaling of population of retinal ganglion cells (RGCs) that account either for emmetropization or refractive errors has still to be elucidated. Thorough knowledge of the underlying mechanisms could provide insight to understanding myopia. In this study, we found that focused and defocused images can change both excitatory and inhibitory conductance of ON alpha, OFF alpha and ON–OFF retinal ganglion cells in the mouse retina. The firing patterns of population of RGCs vary under the different powers of defocused images and can be affected by dopamine receptor agonists/antagonists’ application. OFF-delayed RGCs or displaced amacrine cells (dACs) with time latency of more than 0.3 s had synchrony firing with other RGCs and/or dACs. These spatial synchrony firing patterns between OFF-delayed cell and other RGCs/dACs were significantly changed by defocused image, which may relate to edge detection. The results suggested that defocused images induced changes in the multineuronal firing patterns and whole cell conductance in the mouse retina. The multineuronal firing patterns can be affected by dopamine receptors’ agonists and antagonists. Synchronous firing of OFF-delayed cells is possibly related to edge detection, and understanding of this process may reveal a potential therapeutic target for myopia patients.

scholarly journals Tracer coupling of intrinsically photosensitive retinal ganglion cells to amacrine cells in the mouse retina

2010 ◽  
Vol 518 (23) ◽  
pp. 4813-4824 ◽  
Author(s):  
Luis Pérez de Sevilla Müller ◽  
Michael Tri H. Do ◽  
King-Wai Yau ◽  
Shigang He ◽  
William H. Baldridge
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Amacrine Cells ◽  
Mouse Retina ◽  
Retinal Ganglion

scholarly journals POU6F2 Positive Retinal Ganglion Cells a Novel Group of ON-OFF Directionally Selective Subtypes in the Mouse Retina

2020 ◽  
Author(s):  
Ying Li ◽  
Jiaxing Wang ◽  
Rebecca King ◽  
Eldon E. Geisert
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Yellow Fluorescent Protein ◽  
Corneal Thickness ◽  
Amacrine Cells ◽  
Molecular Signature ◽  
Retinal Cell ◽  
Mouse Retina ◽  
Inner Plexiform Layer ◽  
Retinal Ganglion

AbstractPurposePreviously we identified POU6F2 as a genetic link between central corneal thickness (CCT) and risk of open-angle glaucoma. The present study is designed to characterize the POU6F2-positive retinal ganglion cells (RGCs).MethodsThe Thy1-YFP-H mouse was used to identify the structure of POU6F2-positive RGCs in the retina. In the retina of the Thy1-YFP-H mouse approximately 3% of the RGCs were labeled with yellow fluorescent protein. These retinas were stained for POU6F2 to identify the morphology of the POU6F2 subtypes in 3D reconstructions of the labeled RGCs. Multiple retinal cell markers were also co-stained with POU6F2 to characterize the molecular signature of the POU6F2-positive RGCs. DBA/2J glaucoma models were used to test the role of POU6F2 in injury.ResultsIn the retina POU6F2 labels 32.9% of the RGCs in the DBA/2J retina (16.1% heavily and 16.8% lightly labeled). In 3D constructions of Thy1-YFP-H positive RGCs, the heavily labeled POU6F2-positive cells had dendrites in the inner plexiform layer that were bistratified and appeared to be ON-OFF directionally selective cells. The lightly labeled POU6F2 RGCs displayed 3 different dendritic distributions, with dendrites in the ON sublaminae only, OFF sublaminae only, or bistratified. The POU6F2-positive cells partially co-stained with Cdh6. The POU6F2-positive cells do not co-stain with CART and SATB2 (markers for ON-OFF directionally selective RGC), SMI32 (a marker for alpha RGCs), or ChAT and GAD67(markers for amacrine cells). The POU6F2-positive cells were sensitive to injury. In DBA/2J glaucoma model, at 8 months of age there was a 22% loss of RGCs (labeled with RBPMS) while there was 73% loss of the heavily labeled POU6F2 RGCs.ConclusionsPOU6F2 is a marker for a novel group of RGC subtypes that are ON-OFF directionally selective RGCs that are sensitive to glaucomatous injury.

scholarly journals Optimized culture of retinal ganglion cells and amacrine cells from adult mice

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0242426
Author(s):  
Yong H. Park ◽  
Joshua D. Snook ◽  
Iris Zhuang ◽  
Guofu Shen ◽  
Benjamin J. Frankfort
Keyword(s):  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Culture Media ◽  
Neuronal Cell ◽  
Amacrine Cells ◽  
Mouse Retina ◽  
Neuronal Cultures ◽  
Dependent Manner ◽  
Retinal Ganglion

Cell culture is widely utilized to study the cellular and molecular biology of different neuronal cell populations. Current techniques to study enriched neurons in vitro are primarily limited to embryonic/neonatal animals and induced pluripotent stem cells (iPSCs). Although the use of these cultures is valuable, the accessibility of purified primary adult neuronal cultures would allow for improved assessment of certain neurological diseases and pathways at the cellular level. Using a modified 7-step immunopanning technique to isolate for retinal ganglion cells (RGCs) and amacrine cells (ACs) from adult mouse retinas, we have successfully developed a model of neuronal culture that maintains for at least one week. Isolations of Thy1.2+ cells are enriched for RGCs, with the isolation cell yield being congruent to the theoretical yield of RGCs in a mouse retina. ACs of two different populations (CD15+ and CD57+) can also be isolated. The populations of these three adult neurons in culture are healthy, with neurite outgrowths in some cases greater than 500μm in length. Optimization of culture conditions for RGCs and CD15+ cells revealed that neuronal survival and the likelihood of neurite outgrowth respond inversely to different culture media. Serially diluted concentrations of puromycin decreased cultured adult RGCs in a dose-dependent manner, demonstrating the potential usefulness of these adult neuronal cultures in screening assays. This novel culture system can be used to model in vivo neuronal behaviors. Studies can now be expanded in conjunction with other methodologies to study the neurobiology of function, aging, and diseases.

scholarly journals A noncanonical inhibitory circuit dampens behavioral sensitivity to light

Science ◽  
2020 ◽  
Vol 368 (6490) ◽  
pp. 527-531 ◽  
Author(s):  
Takuma Sonoda ◽  
Jennifer Y. Li ◽  
Nikolas W. Hayes ◽  
Jonathan C. Chan ◽  
Yudai Okabe ◽  
...  
Keyword(s):  
Dynamic Range ◽  
Ganglion Cells ◽  
Gaba Release ◽  
Retinal Ganglion ◽  
Low Light ◽  
Excitatory Neurotransmitter ◽  
Inhibitory Neurotransmitter ◽  
Light Levels ◽  
Behavioral Sensitivity ◽  
Inhibitory Circuit

Retinal ganglion cells (RGCs) drive diverse, light-evoked behaviors that range from conscious visual perception to subconscious, non–image-forming behaviors. It is thought that RGCs primarily drive these functions through the release of the excitatory neurotransmitter glutamate. We identified a subset of melanopsin-expressing intrinsically photosensitive RGCs (ipRGCs) in mice that release the inhibitory neurotransmitter γ-aminobutyric acid (GABA) at non–image-forming brain targets. GABA release from ipRGCs dampened the sensitivity of both the pupillary light reflex and circadian photoentrainment, thereby shifting the dynamic range of these behaviors to higher light levels. Our results identify an inhibitory RGC population in the retina and provide a circuit-level mechanism that contributes to the relative insensitivity of non–image-forming behaviors at low light levels.

Sign in / Sign up

Export Citation Format

Share Document