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.
Highlights
Various hypotheses were raised to account for this centrifugal preference, including the arrangement of starburst amacrine cells (SACs) excitatory inputs, their kinetics, as well as reciprocal inhibition between SACs
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
Summary
Retinal direction selectivity emerges in direction selective retinal ganglion cells (DSGCs), which strongly respond to motion in one (preferred) direction and weakly to motion in the opposite (null) direction (Fig 1A) [1,2,3,4]. The key mechanism for generating direction selectivity in DSGCs is asymmetric GABAergic inhibition from starburst amacrine cells (SACs) [5,6,7] This asymmetry is achieved by asymmetric wiring from SACs to DSGCs [8] combined with the centrifugal (CF) preference of SAC processes (SAC dendrites and axons are synonymous and called processes): SAC processes respond more strongly to motion away from the cell soma (CF) than towards cell soma (centripetal, CP) (Fig 1B and 1C) [9,10,11]. The precise spatiotemporal distribution may contribute to SAC CF preference, as only during centrifugal motion the sequential activation of the sustained and transient inputs is effectively integrated (Fig 1E). This spatiotemporal dependence of excitation has not always been observed in experimental data and its contribution to SAC CF preference remains controversial [11,25]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
