Predicting and Manipulating Cone Responses to Naturalistic Inputs

Abstract

Primates explore their visual environment by making frequent saccades, discrete and ballistic eye movements that direct the fovea to specific regions of interest. Saccades produce large and rapid changes in input. The magnitude of these changes and the limited signaling range of visual neurons mean that effective encoding requires rapid adaptation. Here, we explore how macaque cone photoreceptors maintain sensitivity under these conditions. Adaptation makes cone responses to naturalistic stimuli highly nonlinear and dependent on stimulus history. Such responses cannot be explained by linear or linear-nonlinear models but are well explained by a biophysical model of phototransduction based on well-established biochemical interactions. The resulting model can predict cone responses to a broad range of stimuli and enables the design of stimuli that elicit specific (e.g., linear) cone photocurrents. These advances will provide a foundation for investigating the contributions of cone phototransduction and post-transduction processing to visual function.

Adaptation in cone photoreceptors contributes to an unexpected insensitivity of primate On parasol retinal ganglion cells to spatial structure in natural images

“…These properties are apparent in both the cone current ( Figure 6A , top) and voltage ( Figure 6A , bottom) responses. These properties of the cone responses are created by rapid adaptation in the phototransduction process ( Angueyra et al, 2022 ), due to a light-dependent increase in PDE activity ( Nikonov et al, 2000 ), which causes the gain of the cone light response to be modulated during each cycle of the sinusoid. The cone responses are well captured by an empirically derived biophysical model of cone phototransduction (see Figure 6—figure supplement 1 , Materials and methods and Angueyra et al, 2022 for details).…”

“…A front-end model of cone phototransduction was added to the model for the analyses in Figures 6 — 8 . This model consists of a set of differential equations that capture measured cone responses to a broad range of stimuli ( Angueyra et al, 2022 ; Figure 6—figure supplement 1 ). All parameters of the cone model were set by previous measurements.…”

Systematic reduction of the dimensionality of natural scenes allows accurate predictions of retinal ganglion cell spike outputs

“…Decades of physiological studies, however, have observed that notable nonlinearities occur in both space and time. Temporally, photoreceptor responses are strongly shaped by adaptation and hence are poorly described by linear models ( 34 – 36 ). Spatially, bipolar cells rectify (a nonlinear process) the signals that provide inputs to RGCs ( 9 , 10 , 12 ).…”

Analysis of calcium dynamics for dim-light responses in rod and cone photoreceptors

“…In this work, we derived analytic results for dim-light responses in rods and cones that show how response sensitivity and dynamics change as the Ca 2+ kinetics is altered due to fast buffering and change in the extracellular Ca 2+ concentration. Our analytic formulas not only provide quantitative and conceptual insight, but they are also a means to easily compute photoreceptor responses based on underlying biophysical parameters without having to numerically solve a system of differential equations, which can be used as input to study downstream processes in the retina [59].…”