Rod Noise Research Articles

Controlling the Gain of Rod-Mediated Signals in the Mammalian Retina

Effective sensory processing requires matching the gain of neural responses to the range of signals encountered. For rod vision, gain controls operate at light levels at which photons arrive rarely at individual rods, light levels too low to cause adaptation in rod phototransduction. Under these conditions, adaptation within a conserved pathway in mammalian retina maintains sensitivity as light levels change. To relate retinal signals to behavioral work on detection at low light levels, we measured how background light affects the gain and noise of primate ganglion cells. To determine where and how gain is controlled, we tracked rod-mediated signals across the mouse retina. These experiments led to three main conclusions: (1) the primary site of adaptation at low light levels is the synapse between rod bipolar and AII amacrine cells; (2) cellular noise after the gain control is nearly independent of background intensity; and (3) at low backgrounds, noise in the circuitry, rather than rod noise or fluctuations in arriving photons, limits ganglion cell sensitivity. This work provides physiological insights into the rich history of experiments characterizing how rod vision avoids saturation as light levels increase.

Molecular Mechanism of Spontaneous Pigment Activation in Retinal Cones

Spontaneous current and voltage fluctuations (dark noise) in the photoreceptor cells of the retina limit the ability of the visual system to detect dim light. We recorded the dark current noise of individual salamander L cones. Previous work showed that the dark noise in these cells arises from thermal activation of the visual pigment. From the temperature dependence of the rate of occurrence of elementary noise events, we found an Arrhenius activation energy Ea of 25±7 kcal/mol (mean±SD). This Ea is similar to that reported for the thermal isomerization of 11-cis retinal in solution, suggesting that the cone pigment noise results from isomerization of the retinal chromophore. Ea for the cone noise is similar to that previously reported for the “photon-like” noise of rods, but the preexponential factor is five orders of magnitude higher. To test the hypothesis that thermal isomerization can only occur in molecules whose Schiff base linkage is unprotonated, we changed the pH of the solution bathing the cone outer segment. This had little effect on the rate of occurrence of elementary noise events. The rate was also unchanged when the cone was exposed to Ringer solution made up from heavy water, whose solvent isotope effect should reduce the probability, that the Schiff base nitrogen is naked.

Rod pigment and rod noise in the European toad Bufo bufo

Behavioural experiments and ganglion cell recordings indicate that the visual sensitivity of dark-adapted toads is limited by the occurrence of spontaneous isomerization-like noise events in the rods. The frequency of these “false photons” has previously been studied (with micropipette recording) in the toad species Bufo marinusm, while the behavioural thresholds were determined using Bufo bufo toads. Thus, it was necessary to check that the noise event frequency is roughly the same in these two species. Here we show that it is, in both species, close to 0.02 events per second and rod (at 22°C). Using microspectrophotometry we further show that the absorption spectra of these two rhodopsins are very similar, peaking around 503.3 and 501.8 nm for B. marinus and B. bufo, respectively.

Photic Environment, Visual Pigments, and the Limits of the Visible Spectrum

The limits of the visible spectrum are set by the light available for vision, and by the visual pigment absorbance. The hundreds of visual pigments studied to the present day have absorbance maxima spread within the range from 350 to 620 nm. Yet this diversity is used for vision quite nonuniformly: rod and cone visual pigments are tightly clustered around a few preferred positions in the spectrum, eg near 500 nm in the rods of land animals. The so-called ‘sensitivity hypothesis’ assumes that the clustering is to maximise the number of absorbed photons available in the animals' light environment. In most cases, however, visual pigments are substantially more short-wave (blue-shifted) than is necessary for maximum quantal absorption. Examples of the ‘blue shift’ are the Purkinje shift during cone - rod transition in dark adaptation, the hypsochromic shift of rod visual pigments in deep-water fish, and a similar shift in the cone pigments of geckos and some snakes as a result of evolutionary adaptation to nocturnal habits. It is argued that an important limiting factor in vision is the dark noise produced by thermal isomerisation of the chromophore. Measurements of the dark noise in rods with different visual pigments show that the noise increases steeply when the absorbance maximum is shifted to longer wavelengths, thus precluding the use of long-wave pigments for vision at low intensities. The optimum spectral position of a pigment may be that which ensures a maximum light-to-noise ratio in a particular photic environment.

Molecular origin of continuous dark noise in rod photoreceptors

Noise in the rod photoreceptors limits the ability of the dark-adapted visual system to detect dim lights. We investigated the molecular mechanism of the continuous component of the electrical dark noise in toad rods. Membrane current was recorded from intact, isolated rods or truncated, internally dialyzed rod outer segments. The continuous noise was separated from noise due to thermal activation of rhodopsin and to transitions in the cGMP-activated channels. Selectively disabling different elements of the phototransduction cascade allowed examination of their contributions to the continuous noise. These experiments indicate that the noise is generated by spontaneous activation of cGMP phosphodiesterase (PDE) through a process that does not involve transducin. The addition of recombinant gamma, the inhibitory subunit of PDE, did not suppress the noise, indicating that endogenous gamma does not completely dissociate from the catalytic subunit of PDE during spontaneous activation. Quantitative analysis of the noise provided estimates of the rate constants for spontaneous PDE activation and deactivation and the catalytic activity of a single PDE molecule in situ.

Ganglion cell performance at absolute threshold in toad retina: effects of dark events in rods.

1. The performance of ganglion cells in detecting flashes of light near the absolute threshold was studied in an isolated eye-cup preparation of toad retina. Retinal ganglion cells, through which all visual information from the rods must flow to the brain, are in a key position for evaluating the still unproven hypothesis that the absolute light sensitivity is limited by rod noise (Barlow, 1956). 2. The dark-adapted threshold intensity for these cells, which were selected on the basis of their high sensitivity, averaged 0.029 Rh* flash-1 (range 0.008-0.062), where Rh* signifies one photoisomerization per rod. On average, 46 photoisomerizations were needed per receptive field per flash to evoke a threshold response (range 16-84). 3. In the threshold region, frequency of responses versus mean flash intensity was determined. Threshold performance could be described by theoretical frequency of response curves, allowing intrinsic noise to be estimated in terms of an equivalent rate of photoisomerization-like (dark) events. In two completely characterized cells the rate of dark events corresponded to 0.03 and 0.06 Rh*DS-1, where Rh*D signifies one dark event per rod. 4. Threshold elevations produced by dim backgrounds were studied. The results of these experiments are consistent with a dark event rate equivalent to 0.046 Rh*DS-1, or 0.037 Rh*DS-1 after correcting for a probable decrease in summation time. 5. The rate of actual dark events (0.028 Rh*DS-1, 20 degrees C) measured in Bufo rods (Baylor, Lamb & Yau, 1980) is close to the equivalent rates determined here. Thus, for the ganglion cells signalling the dimmest lights, the dark events in rods appear to be the most significant intrinsic retinal noise source limiting detection.