Abstract
Purpose :
The intrinsic noise of the sensory transduction cascade sets fundamental limits for signal detection in sensory neurons. Indeed, the rod phototransduction cascade displays two forms of dark noise called discrete and continuous noise. Thediscrete noise is thought to originate from spontaneous activation of rhodopsin (Rh). Continuous noise has been proposed to be generated in the downstream signaling cascade. Both types of noise have been proposed to limit some aspects of single photon detection in rod photoreceptors. However, it is not clear which form of noise ultimately limits visual perception.
Methods :
In our study, we used several mouse strains that express altered concentration of key phototransduction proteins, namely Rh, Transducin (Tr) and phosphodiesterase (PDE6), or a modulatory protein of PDE activity (GARP2 KO mice). We recorded discrete and continuous noise in rods using the single cell patch clamp technique. In the same mice, we analyzed how the synaptic transmission between rods and rod bipolar cells (RBCs) is altered by these manipulations, using the perforated patch technique.
Results :
Rh heterozygous rods indeed express half the amount of Rh, resulting in a reduction of the discrete noise events by half. No alterations of continuous noise were detected in these rods, or in Tr heterozygous mice. On the other hand, halving PDE concentration leads to a significant change in continuous noise. Interestingly, our preliminary results suggest that GARP2 KO mice show a reduction in dark noise, demonstrating the importance of controlling the activity of spontaneous PDE activity for proper single photon detection.
Conclusions :
Our results suggest that spontaneous thermal activation of rhodopsin indeed is the source of the discrete noise. Moreover, we demonstrate that continuous noise originates in spontaneous activation of PDE and the cGMP turnover rate. Our mouse models will serve as a critical tool to determine the limiting noise that sets detection threshold in the retina near the absolute limits for vision, currently under investigation.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.