Realistic retinal modeling unravels the differential role of excitation and inhibition to starburst amacrine cells in direction selectivity

• Main Authors: Amsalem, O. (Author), Ankri, L. (Author), Ezra-Tsur, E. (Author), Patil, P. (Author), Rivlin-Etzion, M. (Author), Segev, I. (Author)
• Format: Article
• Language: English
• Published: Public Library of Science 2021
• Subjects: algorithm; Algorithms; Amacrine Cells; animal; Animals; article; biological model; biology; Computational Biology; embedding; excitation; genetic algorithm; human cell; kinetics; Mice; Models, Neurological; mouse; physiology; retina; Retina; retina amacrine cell; retina ganglion cell; Retinal Ganglion Cells; Visual Pathways; visual system
• Online Access: View Fulltext in Publisher

 Retinal direction-selectivity originates in starburst amacrine cells (SACs), which display a centrifugal preference, responding with greater depolarization to a stimulus expanding from soma to dendrites than to a collapsing stimulus. Various mechanisms were hypothesized to underlie SAC centrifugal preference, but dissociating them is experimentally challenging and the mechanisms remain debatable. To address this issue, we developed the Retinal Stimulation Modeling Environment (RSME), a multifaceted data-driven retinal model that encompasses detailed neuronal morphology and biophysical properties, retina-tailored connectivity scheme and visual input. Using a genetic algorithm, we demonstrated that spatiotemporally diverse excitatory inputs–sustained in the proximal and transient in the distal processes–are sufficient to generate experimentally validated centrifugal preference in a single SAC. Reversing these input kinetics did not produce any centrifugal-preferring SAC. We then explored the contribution of SAC-SAC inhibitory connections in establishing the centrifugal preference. SAC inhibitory network enhanced the centrifugal preference, but failed to generate it in its absence. Embedding a direction selective ganglion cell (DSGC) in a SAC network showed that the known SAC-DSGC asymmetric connectivity by itself produces direction selectivity. Still, this selectivity is sharpened in a centrifugal-preferring SAC network. Finally, we use RSME to demonstrate the contribution of SAC-SAC inhibitory connections in mediating direction selectivity and recapitulate recent experimental findings. Thus, using RSME, we obtained a mechanistic understanding of SACs’ centrifugal preference and its contribution to direction selectivity. Copyright: © 2021 Ezra-Tsur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.