Spatiotemporal properties of glutamate input support direction selectivity in the dendrites of retinal starburst amacrine cells

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    Evaluation Summary:

    This is an important paper that addresses a key mechanism that underlies the canonical computation of direction selectivity in the retina. By using fluorescence imaging of glutamate release from excitatory interneurons combined with a computational model of dendritic integration, the authors make a convincing case that the kinetics of glutamate release contributes to the direction-selectivity of individual neural processes in retinal neurons. This work will appeal to visual neuroscientists as well as cellular physiologists interested in dendritic computations.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

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Abstract

The asymmetric summation of kinetically distinct glutamate inputs across the dendrites of retinal ‘starburst’ amacrine cells is one of the several mechanisms that have been proposed to underlie their direction-selective properties, but experimentally verifying input kinetics has been a challenge. Here, we used two-photon glutamate sensor (iGluSnFR) imaging to directly measure the input kinetics across individual starburst dendrites. We found that signals measured from proximal dendrites were relatively sustained compared to those measured from distal dendrites. These differences were observed across a range of stimulus sizes and appeared to be shaped mainly by excitatory rather than inhibitory network interactions. Temporal deconvolution analysis suggests that the steady-state vesicle release rate was ~3 times larger at proximal sites compared to distal sites. Using a connectomics-inspired computational model, we demonstrate that input kinetics play an important role in shaping direction selectivity at low stimulus velocities. Taken together, these results provide direct support for the ‘space-time wiring’ model for direction selectivity.

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  1. Author Response

    Reviewer #1 (Public Review):

    According to the space-time wiring hypothesis proposed by (Kim, Greene et al. 2014), the BC-off SAC circuit mimics the structure of a Reichardt detector; BCs closer to SAC soma have slower dynamics (they can be more sustained, have a delay in activation or slower rise time), while BCs further away are more transient. Later studies confirmed the connectivity and expanded the model on SACs (Ding, Smith et al. 2016, Greene, Kim et al. 2016). However, physiological studies that used somatic recordings to assess the BC properties at different dendritic distances were inconclusive (Stincic, Smith et al. 2016, Fransen and Borghuis 2017). Here, the authors used iGluSnFR, a glutamate sensor to measure the signals impinging on SAC dendrites. Their experimental findings align with the space-time …

  2. Evaluation Summary:

    This is an important paper that addresses a key mechanism that underlies the canonical computation of direction selectivity in the retina. By using fluorescence imaging of glutamate release from excitatory interneurons combined with a computational model of dendritic integration, the authors make a convincing case that the kinetics of glutamate release contributes to the direction-selectivity of individual neural processes in retinal neurons. This work will appeal to visual neuroscientists as well as cellular physiologists interested in dendritic computations.

    (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

  3. Reviewer #1 (Public Review):

    According to the space-time wiring hypothesis proposed by (Kim, Greene et al. 2014), the BC-off SAC circuit mimics the structure of a Reichardt detector; BCs closer to SAC soma have slower dynamics (they can be more sustained, have a delay in activation or slower rise time), while BCs further away are more transient. Later studies confirmed the connectivity and expanded the model on SACs (Ding, Smith et al. 2016, Greene, Kim et al. 2016). However, physiological studies that used somatic recordings to assess the BC properties at different dendritic distances were inconclusive (Stincic, Smith et al. 2016, Fransen and Borghuis 2017). Here, the authors used iGluSnFR, a glutamate sensor to measure the signals impinging on SAC dendrites. Their experimental findings align with the space-time wiring hypothesis, …

  4. Reviewer #2 (Public Review):

    The authors present a nice series of imaging experiments confirming previous anatomical and electrophysiological evidence for the "space-time wiring" model for directionally selective responses in SAC dendrites. Fluorescence measurements with a genetically encoded glutamate indicator show that excitatory inputs to proximal SAC dendrites are more sustained than distal dendrites. Although the signals are shaped by surround inhibition, the fundamental differences persist with inhibition blocked, suggesting intrinsic differences in the synaptic release processes in different cone bipolar cell types.

    The authors examine iGluSnFR dynamics in individual SACs (Figure 1) and in a population of SACs (Figure 2). The latter is possible because distal inputs to all SACs occur deeper in the IPL and so can be imaged …

  5. Reviewer #3 (Public Review):

    In the study "Spatiotemporal properties of glutamate input support direction selectivity in the dendrites of retinal starburst amacrine cells", Srivastava, deRosenroll, and colleagues study the role of excitatory inputs in generating direction selectivity in the mouse retina. Computational and anatomical studies have suggested that the "space-time-wiring" model contributes to direction-selective responses in the mammalian retina. This model relies on temporally distinct excitatory inputs that are offset in space, thereby yielding stronger responses for motion in one versus the other direction. Conceptually, this is similar to the Reichardt detector of motion detection proposed many decades ago. So far, however, there is little functional evidence for the implementation of the space-time-wiring model.

    Here, …