Abstract
Purpose :
Rod photoreceptors in the retina are optimized to detect dim light stimuli, even single photons. However, the ability of rods to reliably relay quantal events to the second order rod bipolar cells (RBCs) is affected by two forms of dark noise, discrete and continuous noise, intrinsically present in the phototransduction signaling cascade. Spontaneous activation of rhodopsin (Rh) is believed to be the origin of discreate noise, whereas continuous noise is thought to originate downstream of Rh activation. It is not clear which form of noise ultimately limits visual perception and exactly how they are processed by the retinal circuitry. The aim of our work is to determine which form of noise sets fundamental limits to detection near absolute visual threshold.
Methods :
We took advantage of genetically modified mouse strains that display different levels of expression of key phototransduction proteins. Experiments were performed on rhodopsin heterozygous mice (Rh+/-), phosphodiesterase heterozygous mice (PDE6+/-) and knock out mice for a modulatory protein of the basal activity of PDE6 (GARP2 KO). Using the perforated whole cell patch clamp technique, we recorded single photon responses and dark noise in rods and RBCs and extracted signal to noise ratios (SNR). In the same mice, we performed a new behavioral test to determine behavioral detection threshold.
Results :
Rh+/- rods indeed express half the amount of Rh, resulting in a reduction of discrete noise events by half. GARP2 KO rods displayed a decrease in continuous noise and both rods and RBCs showed an increase in SNR. Interestingly, PDE6 +/- rods, despite showing an increase in continuous noise, did not show a significant change in SNR. Preliminary results from our behavioral test suggest that modifying both discreate and continuous noise can affect visual detection threshold.
Conclusions :
Our results suggest that increasing basal activation of PDE6 results in an increase in SNR in both rods and RBCs, with a modest effect on visual detection threshold. Interestingly, reducing the amount of Rh in rods does not affect SNR at the level of RBC and the first visual synapse, but will increase behavioral detection threshold compared to WT mice. Our results gives new insights into the SNR processing in the retinal circuitry and its effect on visually guided behavior.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.