Retinal degeneration increases inter-trial variabilities of light-evoked spiking activities in ganglion cells

Abstract

Retinal ganglion cells (RGCs) transmit visual information to the brain in the form of spike trains, which form visual perception. The reliabilities of spike timing and count are thought to play a crucial role in generating stable percepts. However, the effect of retinal degeneration on spike reproducibility remains underexplored. In this study, we examined longitudinal changes of both spike timing and count across different RGC types in response to repeated presentations of an identical light stimulus in retinal degeneration 10 (rd10) mice (B6.CXBl-Pde6b^rd10/J), a well-established model of retinitis pigmentosa (RP).

We recorded the spiking responses of RGC populations to repeated white flashes using 256-channel multi-electrode array (MEA) at four rd10 age groups representing various stages of retinal degeneration. Our experimental results revealed a significant reduction in both spike timing and count consistencies compared to those in wild-type RGC recordings. Furthermore, the inter-trial variability patterns of different RGC types were found to differ throughout the degeneration process. For instance, when the spike time tiling coefficient (STTC) was used to evaluate inter-trial spike timing consistency, contrast-sensitive RGCs (ON, OFF, and ON-OFF types) exhibited a systematic decrease in spike timing consistency as degeneration progressed, whereas the remaining units did not show similar trends. Thus, we concluded that light-evoked spike trains become less consistent as degeneration progresses, with variability in spike timing and spike count varying across cell types.

Given the critical role of spiking reliability in visual perception, our findings highlight the importance of accounting for cell type-specific degeneration patterns and inter-trial spiking inconsistencies when developing visual rehabilitation therapies to achieve enhanced performance. The underlying mechanism(s) driving the inter-trial spiking inconsistencies warrant further investigation.