The impact of photoreceptor noise on retinal gain controls

Multiple retinal mechanisms preserve visual sensitivity as the properties of the light inputs change. Rapid gain controls match the effective signaling range of retinal neurons to the local image statistics. Such gain controls trade an increased sensitivity for some aspects of the inputs for a decreased sensitivity to others. Rapid, local gain control comes at another cost: noise in the signal controlling gain (e.g. from the photoreceptors) will cause gain itself to vary even when the statistics of the light input are constant. Recent advances in identifying retinal pathways and the sites and mechanisms of mean and contrast adaptation have begun to clarify the tradeoffs associated with different gain control locations and how these tradeoffs differ for rod and cone vision.     

Light-induced voltage noise in the photoreceptor of Drosophila melanogaster

The Drosophila photoreceptor potential is thought to be composed of discrete unit potentials called bumps. The steady-state receptor potential and the accompanying voltage fluctuations were recorded intracellularly under steady illumination. The occurrence rate, effective amplitude, and duration of the bumps were deduced by assuming a shot noise model. Over a wide range of light intensity, the duration of bumps remained essentially constant (25-30 ms). Below the saturation intensity for the receptor potential, the bump rate was roughly proportional to the intensity, and the adjustment of bumps to smaller size at higher intensity was mainly responsible for the nonlinear behavior of the receptor potential. The reduction in size of bumps at increasing light intensity was found to be due mainly to the diminishing magnitude of the bump current, and not to some other secondary effects. The bump rate saturated at about 3 x 105-106 events/s.     

A spatiotemporal white noise analysis of photoreceptor responses to UV and green light in the dragonfly median ocellus

Adult dragonflies augment their compound eyes with three simple eyes known as the dorsal ocelli. While the ocellar system is known to mediate stabilizing head reflexes during flight, the ability of the ocellar retina to dynamically resolve the environment is unknown. For the first time, we directly measured the angular sensitivities of the photoreceptors of the dragonfly median (middle) ocellus. We performed a second-order Wiener Kernel analysis of intracellular recordings of light-adapted photoreceptors. These were stimulated with one-dimensional horizontal or vertical patterns of concurrent UV and green light with different contrast levels and at different ambient temperatures. The photoreceptors were found to have anisotropic receptive fields with vertical and horizontal acceptance angles of 15 degrees and 28 degrees, respectively. The first-order (linear) temporal kernels contained significant undershoots whose amplitudes are invariant under changes in the contrast of the stimulus but significantly reduced at higher temperatures. The second-order kernels showed evidence of two distinct nonlinear components: a fast acting self-facilitation, which is dominant in the UV, followed by delayed self- and cross-inhibition of UV and green light responses. No facilitatory interactions between the UV and green light were found, indicating that facilitation of the green and UV responses occurs in isolated compartments. Inhibition between UV and green stimuli was present, indicating that inhibition occurs at a common point in the UV and green response pathways. We present a nonlinear cascade model (NLN) with initial stages consisting of separate UV and green pathways. Each pathway contains a fast facilitating nonlinearity coupled to a linear response. The linear response is described by an extended log-normal model, accounting for the phasic component. The final nonlinearity is composed of self-inhibition in the UV and green pathways and inhibition between these pathways. The model can largely predict the response of the photoreceptors to UV and green light.     

The limit of photoreceptor sensitivity: molecular mechanisms of dark noise in retinal cones

Detection threshold in cone photoreceptors requires the simultaneous absorption of several photons because single photon photocurrent is small in amplitude and does not exceed intrinsic fluctuations in the outer segment dark current (dark noise). To understand the mechanisms that limit light sensitivity, we characterized the molecular origin of dark noise in intact, isolated bass single cones. Dark noise is caused by continuous fluctuations in the cytoplasmic concentrations of both cGMP and Ca(2+) that arise from the activity in darkness of both guanylate cyclase (GC), the enzyme that synthesizes cGMP, and phosphodiesterase (PDE), the enzyme that hydrolyzes it. In cones loaded with high concentration Ca(2+) buffering agents, we demonstrate that variation in cGMP levels arise from fluctuations in the mean PDE enzymatic activity. The rates of PDE activation and inactivation determine the quantitative characteristics of the dark noise power density spectrum. We developed a mathematical model based on the dynamics of PDE activity that accurately predicts this power spectrum. Analysis of the experimental data with the theoretical model allows us to determine the rates of PDE activation and deactivation in the intact photoreceptor. In fish cones, the mean lifetime of active PDE at room temperature is approximately 55 ms. In nonmammalian rods, in contrast, active PDE lifetime is approximately 555 ms. This remarkable difference helps explain why cones are noisier than rods and why cone photocurrents are smaller in peak amplitude and faster in time course than those in rods. Both these features make cones less light sensitive than rods.     

Spatial information capacity of eyes: Roles of Na+ channels and photon noise in photoreceptor

The spatial information capacity of the human eye for photopic vision has been determined taking into account the intensity response function of the photoreceptor. It has been found that spatial information capacity increases with the mean luminance upto a certain value of mean luminance and after that it starts decreasing. The decrement occurs below the damage threshold. These results are in agreement with the reported experimental observations. It has been concluded that the limited number of Na⁺ channels in the photoreceptor outer segment and the photon noise are responsible for the fall in the information capacity below the damage threshold.Associated with the Biochemistry Cell     

The intracellular pupil mechanism and photoreceptor signal: noise ratios in the fly Lucilia cuprina

The function of the intracellular pupil mechanism is examined by comparing the responses of photoreceptors in normal flies with those from white-eyed flies that lack the pupil. In white-eyed flies the response to an intensity increment of fixed contrast decreases at high background intensities. There is a smaller decrease in noise amplitude so that the signal:noise ratio falls. The intensity dependence of the photoreceptor signal:noise ratio fits a simple model in which activated photopigment molecules compete for 3 X 10(4) transduction units. The signal:noise ratio decreases at high intensities because the transduction units are saturated. This model is supported by a noise analysis, which provides three estimates of the number of events generating photoreceptor responses. In white-eyed flies the event number saturates at high background intensities, suggesting that a maximum of 2 X 10(4) events can be simultaneously active. Wild-type flies do not exhibit saturation effects over the range of intensities studied. The signal:noise ratio rises with intensity to reach a stable asymptote, close to the maximum observed for white-eyed flies. Pupil attenuation is calculated from measurements of signal:noise ratio in white-eyed and wild-type flies. The pupil is progressively activated over a two log unit intensity range and when fully closed attenuates the effective intensity by 99%. The threshold of this pupil effect coincides with the threshold of pupil activation measured optically. We conclude that the intracellular pupil attenuates the light flux to prevent receptor saturation and to extend the range of intensities at which fly photoreceptors operate close to their maximum signal:noise ratio. This upper limit is determined by the number of transduction units generating a cell's response.     

Physical analysis of light-scattering changes in bovine photoreceptor membrane suspensions.

We have used electron microscopy and model calculations to analyze the physical basis of light-scattering signals from suspensions of photoreceptor membranes. These signals have previously been used to probe interactions between photoactivated rhodopsin (R*) and the peripheral membrane enzyme, GTP-binding protein (G) (Kühn et al., 1981, Proc. Natl. Acad. Sci. USA., 78:6873-6877). Although there is no unique physical interpretation of these signals, we have shown in this study that they were qualitatively unchanged when the rod outer segment fragments (containing stacked disks) were fragmented by sonication or osmotic shock to produce spherical disk membrane vesicles. An exact treatment of the scattering process for spherical vesicles enabled us to evaluate the effects of changing membrane thickness, refractive index, or vesicle diameter. We present a particular redistribution of mass upon R*-G interaction that fits the experimental data.     

Signal/noise analysis of FRET-based sensors

Molecular sensors based on intramolecular Förster resonance energy transfer (FRET) have become versatile tools to monitor regulatory molecules in living tissue. However, their use is often compromised by low signal strength and excessive noise. We analyzed signal/noise (SNR) aspects of spectral FRET analysis methods, with the following conclusions: The most commonly used method (measurement of the emission ratio after a single short wavelength excitation) is optimal in terms of signal/noise, if only relative changes of this uncalibrated ratio are of interest. In the case that quantitative data on FRET efficiencies are required, these can be calculated from the emission ratio and some calibration parameters, but at reduced SNR. Lux-FRET, a recently described method for spectral analysis of FRET data, allows one to do so in three different ways, each based on a ratio of two out of three measured fluorescence signals (the donor and acceptor signal during a short-wavelength excitation and the acceptor signal during long wavelength excitation). Lux-FRET also allows for calculation of the total abundance of donor and acceptor fluorophores. The SNR for all these quantities is lower than that of the plain emission ratio due to unfavorable error propagation. However, if ligand concentration is calculated either from lux-FRET values or else, after its calibration, from the emission ratio, SNR for both analysis modes is very similar. Likewise, SNR values are similar, if the noise of these quantities is related to the expected dynamic range. We demonstrate these relationships based on data from an Epac-based cAMP sensor and discuss how the SNR changes with the FRET efficiency and the number of photons collected.     

Theoretical conformational analysis of phospholipids bilayers

We present a computational approach describing the conformation of lipid molecules (1-2-dipalmitoyl-sn-glycero-3 phosphocholine (DPPC)) organized in bilayers. The classical semi-empirical method used in peptide conformational analysis has been extended successfully to lipids. The excellent agreement between our theoretical predictions and recent experimental data on the molecular organization of lipid bilayers suggests that the method could be a valuable tool in the lipid conformational analysis but also in the prediction of orientation and mode of insertion of amphiphilic molecules into the lipid bilayer.     

Theoretical conformation analysis of MCD peptide

The spatial structure of the MCD-peptide from bee venom has been calculated basing on the known sequence of 22 amino acid. The a priori calculations produce a system of two disulfide bonds, identical to that observed in the native structure. The calculated structure of MCD-peptide is close to that proposed earlier for the homologues peptide tertiapin and is confirmed by NMR and CD data.     

Theoretical analysis of chest wall mechanics

A mathematical model of the chest wall partitioned into rib cage, diaphragmatic and abdominal components is developed consistent with published experimental observations. The model describes not only the orthodox chest wall movements (rib cage and abdomen expand together during inspiration) of the quietly breathing standing adult, but also Mueller maneuvers (inspiration against an occluded airway opening) and the paradoxical breathing patterns (rib cage contracts while abdomen expands during inspiration) observed in quadriplegia and in the newborn. The abdomen is inferred to act as a cylinder reinforced by the abdominal muscles functioning similarly to bands around a barrel. The rib cage and abdominal wall are inferred to act not as though they were directly attached to one another, but as though they were being pressed together by the skeleton. Furthermore, transabdominal pressure is visualized as acting, not across the rib cage isolated from the diaphragm, as has been suggested previously, but instead, across the combined rib cage and diaphragm acting as a deformable unit containing the lungs.     

Theoretical analysis of mixed irradiation.

We revised the models for mixed irradiation by Zaider and Rossi and by Suzuki, substituting second-order repair function for a first-order one in reduction and interaction factors of the models. The reduction factor, which reduces the contribution of the square of a dose to cell killing in the models, and the interaction factor, which also reduces the contribution of the interaction of two or more doses of different types of radiation, were formulated by using the second-order repair function. These newly modified models for mixed irradiation can express or predict cell survival more accurately than the older ones, especially when irradiation is prolonged at low dose rates.