Two mechanisms for direction selectivity in a model of the primate starburst amacrine cell

Abstract

In a recent study, visual signals were recorded for the first time in starburst amacrine cells of the macaque retina, and, as for mouse and rabbit, a directional bias observed in calcium signals was recorded from near the dendritic tips. Stimulus motion from the soma toward the tip generated a larger calcium signal than motion from the tip toward the soma. Two mechanisms affecting the spatiotemporal summation of excitatory postsynaptic currents have been proposed to contribute to directional signaling at the dendritic tips of starbursts: (1) a “morphological” mechanism in which electrotonic propagation of excitatory synaptic currents along a dendrite sums bipolar cell inputs at the dendritic tip preferentially for stimulus motion in the centrifugal direction; (2) a “space–time” mechanism that relies on differences in the time-courses of proximal and distal bipolar cell inputs to favor centrifugal stimulus motion. To explore the contributions of these two mechanisms in the primate, we developed a realistic computational model based on connectomic reconstruction of a macaque starburst cell and the distribution of its synaptic inputs from sustained and transient bipolar cell types. Our model suggests that both mechanisms can initiate direction selectivity in starburst dendrites, but their contributions differ depending on the spatiotemporal properties of the stimulus. Specifically, the morphological mechanism dominates when small visual objects are moving at high velocities, and the space–time mechanism contributes most for large visual objects moving at low velocities.

Heterogeneous presynaptic receptive fields contribute to directional tuning in starburst amacrine cells

“…Figure 9 illustrates the peak DS index achieved with EAs trained to find the postsynaptic properties (axial resistance, leak, and voltage-gated calcium channel conductance) that lead to optimal directional performance for all possible proximal and distal functional cluster placement combinations. In line with prior work ( Fransen and Borghuis, 2017 ; Kim et al, 2014 ; Srivastava et al, 2022 ; Stincic et al, 2016 ; Wu et al, 2023 ), the optimal DS was attained when proximal BCs with sustained waveforms were combined with transient distal cells. For ON-SACs, the highest DSI = 17 ± 2% was observed with inputs from ON-C6 (proximal) and ON-C2 (distal).…”

“…However, the solution is unstable as the DSI is exceedingly sensitive to minor perturbations in local voltage. Consequently, while threshold-based mechanisms can be highly effective, they are also notably susceptible to noise ( Tukker et al, 2004 ; Wu et al, 2023 ).…”

Heterogeneous presynaptic receptive fields contribute to directional tuning in starburst amacrine cells

“…Figure 9 illustrates the peak DS index achieved with evolutionary algorithms trained to find the postsynaptic properties (axial resistance, leak, and voltage-gated calcium channel conductance) that lead to optimal directional performance for all possible proximal and distal functional cluster placement combinations. In line with prior work (Fransen & Borghuis, 2017;Kim et al, 2014;Srivastava et al, 2022;Stincic et al, 2016;Wu et al, 2023), the optimal DS was attained when proximal BCs with sustained waveforms were combined with transient distal cells. For ON-SACs, the highest DSI = 17 ± 2% was observed with inputs from ON-C6 (proximal) and ON-C2 (distal).…”

“…Consequently, the levels of DS obtained in these simulations did not significantly differ from the findings of the simple proximal-distal parameter exploration presented earlier (ON-SACs: DSI = 17 ± 5%, OFF-SACs: DSI = 21 ± 6%, Figure 10C-F). Based on these results, we can conclude that optimal combination of excitatory signals has the potential to triple the level of directional tuning over SAC-intrinsic mechanisms (Figure 10D, F) (Tukker et al, 2004;Vlasits et al, 2016;Wu et al, 2023).…”

“…This discrepancy suggests that, while suboptimal, motion responses within the bipolar population still offer a more suitable foundation for achieving directional tuning. Notably, Wu et al, 2023, put forward the idea that the spatial arrangement of midget and DB4/5 bipolar cells in the primate retina might contribute to DS computation through a similar space-time wiring mechanism. While we lack information regarding the exact shapes of motion responses in primate bipolar cells, it’s reasonable to speculate that if they exhibit faster dynamics than those observed in mice, the space-time wiring model’s influence on SAC function in primates may be even more pronounced.…”