Neuronal morphology impacts optogenetic stimulation precision

Optogenetic stimulation has recently proven effective in partially restoring vision in the human eye, underlining its potential in clinical applications. Using this technique in sensory cortices could leverage the spatial organization of stimulus feature encoding across the cortical surface to artificially induce perception and restore a lost sense. However, achieving precise stimulation to recruit sensory neuronal populations is challenging, as the full spatial extent of neuronal morphology, including distal parts, may contribute to optogenetic activation. In this study, we investigate how morphology impacts spatial stimulation precision using computational neuron models with physiological optogenetic response dynamics. Our results indicate that morphology constrains precision on a scale of several hundred micrometers. We observe a complex dependence of optogenetic responses on stimulation intensity and across different neuron types, resulting in a varying spatial distribution of activated neurons below the cortical surface. We further explore the potential for enhancing precision through preferential somatic opsin expression or improved stimulator design. Our insights help in interpreting existing experimental data and optimizing precision in future optogenetic interventions.