 Realistic retinal modeling unravels the differential role of excitation and inhibition to starburst amacrine cells in direction selectivityElishai Ezra-Tsur, Oren Amsalem, Lea Ankri, Pritish Patil, Idan Segev and Michal Rivlin-Etzion PLOS Computational Biology, 2021, vol. 17, issue 12, 1-31 Abstract: 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.Author summary: Retinal direction selectivity is a canonical example for a computation undertaken by the retina. Starburst amacrine cells (SACs), interneurons in the retina, mediate direction selectivity via two mechanisms: they form asymmetric inhibitory connections with direction selective ganglion cells (DSGCs); and their processes are themselves direction selective, displaying a centrifugal preference. Various hypotheses were raised to account for this centrifugal preference, including the arrangement of SAC excitatory inputs, their kinetics, as well as reciprocal inhibition between SACs. To address this, we developed the Retinal Stimulation Modeling Environment (RSME)–a modeling environment for highly detailed, biologically plausible simulations, tailored to the exploration of neuronal dynamic and visual processing in retinal circuits. We started with exploring the excitation to a single SAC, and found that a precise organization of the input kinetics along SAC processes can generate a centrifugal preference that matched our experimental recordings. We then generated a network of SACs and found that reciprocal inhibition between SACs further enhances the centrifugal preference. Finally, we embedded a DSGC in the network, and dissected the contribution of SAC-DSGC asymmetric connections and SAC centrifugal preference to direction selectivity in DSGC. Date: 2021 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1009754 DOI: 10.1371/journal.pcbi.1009754 Access Statistics for this article More articles in PLOS Computational Biology from Public Library of Science |
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