Efficient incorporation of dendrites into a large-scale cortical model reveals their surprising role in sharpening optogenetic responses

Single-photon optogenetics enables chronic wide-field stimulation of cortex, facilitating large-scale manipulation of neural code to study cortical processing and advance neuroprosthetics. However, access to neural codes organized at fine spatial scales is compromised by the horizontal spread of stimulation-evoked cortical activity. Overcoming this limitation requires a quantitative understanding of the mechanisms contributing to spread, which include light scattering, dendritic activation, and synaptic transmission. We addressed this with morphology-aware simulations of optogenetic stimulation in a functionally-detailed network model of primary visual cortex. We find that synaptic transmission extends activation by 37–50% beyond the illuminated area, while, paradoxically, neuronal morphology sharpens activation, as apical dendrites sample from the superficial cortex, which is less affected by light dispersion. This unexpected sharpening enhances the fidelity of stimulation with spatially distributed patterns. Our study offers guidance for optogenetic interventions targeting topographically organized neural codes and provides a computational testbed to interpret such experiments.