Differential intrinsic firing properties in sustained and transient mouse alpha RGCs match their light response characteristics and persist during retinal degeneration

Abstract

Retinal ganglion cells (RGCs) are the neuronal connections between the eye and the brain conveying multiple features of the outside world through parallel pathways. While there is a large body of literature how these pathways arise in the retinal network, the process of converting presynaptic inputs into RGC spiking output is little understood. In this study, we show substantial differences in the spike generator across three types of alpha RGCs in female and male mice, the αON sustained, αOFF sustained and αOFF transient RGC. The differences in their intrinsic spiking responses match the differences of the light responses across RGC types. While sustained RGC types have spike generators that are able to generate sustained trains of action potentials at high rates, the transient RGC type fired shortest action potentials enabling it to fire high-frequency transient bursts. The observed differences were also present in late-stage photoreceptor-degenerated retina demonstrating long-term functional stability of RGC responses even when presynaptic circuitry is deteriorated for long periods of time. Our results demonstrate that intrinsic cell properties support the presynaptic retinal computation and are, once established, independent of them. Significance Statement Spiking output from retinal ganglion cells (RGCs) has long been thought to be solely determined by synaptic inputs from the retinal network. We show that the cell-intrinsic spike generator varies across RGC populations and therefore that postsynaptic processing shapes retinal spiking output in three types of mouse alpha RGCs (αRGCs). While sustained αRGC types have spike generators that are able to generate sustained trains of action potentials at high rates, the transient αRGC type fired shortest action potentials enabling them to fire high-frequency transient bursts. Computational modeling suggests that intrinsic response differences are not driven by dendritic morphology but by somatodendritc biophysics. After photoreceptor degeneration, the observed variability is preserved indicating stable physiology across the three αRGC types.