A comprehensive model of the phototransduction cascade in mouse rod cells

Invergo, Brandon M.; Dell’Orco, Daniele; Montanucci, Ludovica; Koch, Karl‐Wilhelm; Bertranpetit, Jaume

doi:10.1039/c3mb70584f

Cited by 33 publications

(67 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2N), as expected if melanopsin were a significant determinant of luxotonic behavior. Whereas the MelLow spectrum was also ∼5× dimmer for rods, as their maintained membrane potential should be close to saturation across all of the light levels used here (33), it is most unlikely that they could contribute to encoding the slow change in irradiance. This assumption is consistent with the lack of luxotonic responses under these conditions in Opn4 −/− mice.…”

Section: Resultsmentioning

confidence: 95%

Melanopsin-driven increases in maintained activity enhance thalamic visual response reliability across a simulated dawn

Storchi

Milosavljevic

Eleftheriou

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Twice a day, at dawn and dusk, we experience gradual but very high amplitude changes in background light intensity (irradiance). Although we perceive the associated change in environmental brightness, the representation of such very slow alterations in irradiance by the early visual system has been little studied. Here, we addressed this deficit by recording electrophysiological activity in the mouse dorsal lateral geniculate nucleus under exposure to a simulated dawn. As irradiance increased we found a widespread enhancement in baseline firing that extended to units with ON as well as OFF responses to fast luminance increments. This change in baseline firing was equally apparent when the slow irradiance ramp appeared alone or when a variety of higher-frequency artificial or natural visual stimuli were superimposed upon it. Using a combination of conventional knockout, chemogenetic, and receptor-silent substitution manipulations, we continued to show that, over higher irradiances, this increase in firing originates with inner-retinal melanopsin photoreception. At the single-unit level, irradiance-dependent increases in baseline firing were strongly correlated with improvements in the amplitude of responses to higher-frequency visual stimuli. This in turn results in an up to threefold increase in single-trial reliability of fast visual responses. In this way, our data indicate that melanopsin drives a generalized increase in dorsal lateral geniculate nucleus excitability as dawn progresses that both conveys information about changing background light intensity and increases the signal:noise for fast visual responses. melanopsin | irradiance | neural coding | silent substitution | DREADD

show abstract

Section: Resultsmentioning

confidence: 95%

Melanopsin-driven increases in maintained activity enhance thalamic visual response reliability across a simulated dawn

Storchi

Milosavljevic

Eleftheriou

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…cnga3 or gngt2b). Building on our exquisite understanding on phototransduction in general (Fain et al, 2010;Lamb, 2013;Pergner and Kozmik, 2017;Pugh and Lamb, 1993;Yau and Hardie, 2009), each of these regulatory changes can be quantitatively linked to a specific functional effect (Invergo et al, 2013(Invergo et al, , 2014. In particular, the tonic level of outer segment cGMP is key as it determines the open-probability of cyclicnucleotide gated (CNG) channels which define the cone's dark current to ultimately set the calcium baseline in the cone pedicle through the opening or closing of synaptic voltage gated calcium channels (Fain et al, 2010;Lamb, 2013;Pergner and Kozmik, 2017).…”

Section: Differentialmentioning

confidence: 99%

“…To quantitatively explore how these sum of all relative gene expression changes might affect the interplay of activators and repressors of the phototransduction cascade (Hurley, 1987;Pugh and Lamb, 1993;Pugh et al, 1999), we used a computational model of phototransduction in ciliary photoreceptors (Invergo et al, 2013(Invergo et al, , 2014 (Fig. 6f).…”

Section: Differentialmentioning

confidence: 99%

“…Error bars in s.e.m.. f, Schematic of phototransduction based on ref (Yau and Hardie, 2009), with activators and repressors denoted in green and grey, respectively. g, Simulated current response of SZ and non-SZ UV-cones to 100% dark-and light-contrasts from a 50% contrast background based on ref (Invergo et al, 2014). Non-SZ was based on default model parameters, while SZ uses relatively scaled parameters according to gene expression ratios as in (e).…”

Section: Differentialmentioning

confidence: 99%

See 1 more Smart Citation

Cellular and molecular mechanisms of photoreceptor tuning for prey capture in larval zebrafish

Yoshimatsu

Schröder

et al. 2019

Preprint

View full text Add to dashboard Cite

Correspondence to t. yoshimatsu@sussex.ac.uk and t.baden@sussex.ac.uk In the eye, the function of same-type photoreceptors must be regionally adjusted to process a highly asymmetrical natural visual world. Here we show that UV-cones in the larval zebrafish area temporalis are specifically tuned for UV-bright prey capture in their upper frontal visual field, which uses the signal from a single cone at a time. For this, UV-detection efficiency is regionally boosted 42-fold. Next, in vivo 2-photon imaging, transcriptomics and computational modelling reveal that these cones use an elevated baseline of synaptic calcium to facilitate the encoding of bright objects, which in turn results from expressional tuning of phototransduction genes. Finally, this signal is further accentuated at the level of glutamate release driving retinal networks. These regional differences tally with variations between peripheral and foveal cones in primates and hint at a common mechanistic origin. Together, our results highlight a rich mechanistic toolkit for the tuning of neurons.

show abstract

“…Once the visual cascade was understood as a G-protein-coupled system, known partial steps were increasingly incorporated into schemes of differential equations describing signal transduction (6), eventually including downstream reactions (7,8) and leading to a full simulation of the electrical response.…”

Section: Introductionmentioning

confidence: 99%

Explicit Spatiotemporal Simulation of Receptor-G Protein Coupling in Rod Cell Disk Membranes

Schöneberg

Heck

Hofmann

et al. 2014

Biophysical Journal

View full text Add to dashboard Cite

Dim-light vision is mediated by retinal rod cells. Rhodopsin (R), a G-protein-coupled receptor, switches to its active form (R(∗)) in response to absorbing a single photon and activates multiple copies of the G-protein transducin (G) that trigger further downstream reactions of the phototransduction cascade. The classical assumption is that R and G are uniformly distributed and freely diffusing on disk membranes. Recent experimental findings have challenged this view by showing specific R architectures, including RG precomplexes, nonuniform R density, specific R arrangements, and immobile fractions of R. Here, we derive a physical model that describes the first steps of the photoactivation cascade in spatiotemporal detail and single-molecule resolution. The model was implemented in the ReaDDy software for particle-based reaction-diffusion simulations. Detailed kinetic in vitro experiments are used to parametrize the reaction rates and diffusion constants of R and G. Particle diffusion and G activation are then studied under different conditions of R-R interaction. It is found that the classical free-diffusion model is consistent with the available kinetic data. The existence of precomplexes between inactive R and G is only consistent with the data if these precomplexes are weak, with much larger dissociation rates than suggested elsewhere. Microarchitectures of R, such as dimer racks, would effectively immobilize R but have little impact on the diffusivity of G and on the overall amplification of the cascade at the level of the G protein.

show abstract

A comprehensive model of the phototransduction cascade in mouse rod cells

Cited by 33 publications

References 54 publications

Melanopsin-driven increases in maintained activity enhance thalamic visual response reliability across a simulated dawn

Melanopsin-driven increases in maintained activity enhance thalamic visual response reliability across a simulated dawn

Cellular and molecular mechanisms of photoreceptor tuning for prey capture in larval zebrafish

Explicit Spatiotemporal Simulation of Receptor-G Protein Coupling in Rod Cell Disk Membranes

Contact Info

Product

Resources

About