Abstract
Purpose :
In the retina, signals originating from rod and cone photoreceptors can reach the retinal ganglion cells (RGCs) through different pathways. Recent findings have provided insights into the relative contributions of all three rod pathways and the cone pathways to the light responses of a particular type of RGC: the tOFF αRGC (Jin et al. 2022 Science Adv. 13, abm4491). However, how these different pathways seamlessly merge to control the retinal output under varying lighting conditions and/or the influence of circadian adaptive mechanisms remains largely unknown. This study aims to build a mathematical model of the retinal circuitry which includes realistic representations of the different rod and cone pathways that can be used to study the relative weighting of rod- and cone-derived signals and their routing in retinal circuits under different conditions.
Methods :
We have developed a detailed mathematical model of the mouse retinal network based on morphological and biophysical data mined in the literature. The model includes 38,416 rods, 1,225 cones, 1,600 rod bipolar cells (RBCs), 650 OFF-cone bipolar cells, and 256 AII amacrine cells, distributed in a square-grid spanning 70,685 µm2, close to the dendritic field area of a single tOFF αRGC. Each retinal cell type is implemented using conductance-based models that follow the Hodgkin-Huxley formalism. Simulations are conducted using the simulation environment Brian2.
Results :
Using the model, we found that the absolute threshold of tOFF αRGCs is about 0.01 R*/rod/s. Eliminating the primary rod pathway at the RBC synapse shifts the threshold to about 1 R*/rod/s (secondary rod pathway threshold) when rod/cone coupling is set to 300 pS, and to about 60 R*/rod/s (tertiary rod pathway threshold) when rod/cone coupling is absent (0 pS). Stimulating the cones alone sets the cone threshold in tOFF αRGCs at about 250 R*/rod/s.
Conclusions :
Our mathematical model closely replicates the essential quantitative and qualitative features of the tOFF αRGC dynamics observed in the experimental setting (Jin et al. 2022). These results validate our model and its suitability for further in silico hypothesis testing. We are currently testing the influence of light and circadian adaptive mechanisms on signal processing in retinal circuits and their impact on tOFF αRGC light responses.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.