Biomedical subjects

Alapakkam P Sampath

Publications and source records attributed to Alapakkam P Sampath.

5 recordsLinked to original sources

PubMed2006

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.

Adaptation, Ocular↗

PubMed2005

Recoverin improves rod-mediated vision by enhancing signal transmission in the mouse retina.

Vision in dim light requires that photons absorbed by rod photoreceptors evoke signals that reliably propagate through the retina. We investigated how a perturbation in rod physiology affects propagation of those signals in the retina and ultimately visual sensitivity. Recoverin is a protein in rods that prolongs phototransduction and enhances visual sensitivity. It is not present in neurons postsynaptic to rods, yet we found that light-evoked responses of rod bipolar and ganglion cells were shortened when measured in recoverin-deficient retinas. Unexpectedly, the effect of recoverin on postsynaptic signals could not be explained by its effect on phototransduction. Instead, it is an effect of recoverin downstream of phototransduction in rods that prolongs signal transmission and enhances visual sensitivity. An important implication of our findings is that the recovery phase of the rod photoresponse does not contribute significantly to visual sensitivity near absolute threshold.

Animals↗

PubMed2005

Retinal processing near absolute threshold: from behavior to mechanism.

Vision at absolute threshold is based on signals produced in a tiny fraction of the rod photoreceptors. This requires that the rods signal the absorption of single photons, and that the resulting signals are transmitted across the retina and encoded in the activity sent from the retina to the brain. Behavioral and ganglion cell sensitivity has often been interpreted to indicate that these biophysical events occur noiselessly, i.e., that vision reaches limits to sensitivity imposed by the division of light into discrete photons and occasional photon-like noise events generated in the rod photoreceptors. We argue that this interpretation is not unique and provide a more conservative view of the constraints behavior and ganglion cell experiments impose on phototransduction and retinal processing. We summarize what is known about how these constraints are met and identify some of the outstanding open issues.

Animals↗

PubMed2004

Selective transmission of single photon responses by saturation at the rod-to-rod bipolar synapse.

A threshold-like nonlinearity in signal transfer from mouse rod photoreceptors to rod bipolar cells dramatically improves the absolute sensitivity of the rod signals. The work described here reaches three conclusions about the mechanisms generating this nonlinearity. (1) The nonlinearity is caused primarily by saturation of the feedforward rod-to-rod bipolar synapse and not by feedback from horizontal or amacrine cells. This saturation renders the rod bipolar current insensitive to small changes in transmitter release from the rod. (2) Saturation occurs within the G protein cascade that couples receptors to channels in the rod bipolar dendrites, with little or no contribution from presynaptic mechanisms or saturation of the postsynaptic receptors. (3) Between 0.5 and 2 bipolar transduction channels are open in darkness at each synapse, compared to the approximately 30 channels open at the peak of the single photon response.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2002

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 E(a) of 25 +/- 7 kcal/mol (mean +/- SD). This E(a) 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. E(a) 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.

Animals↗