Spatially displaced excitation contributes to the encoding of interrupted motion by the retinal direction-selective circuit

  1. Jennifer Ding
  2. Albert Chen
  3. Janet Chung
  4. Hector Acaron Ledesma
  5. Mofei Wu
  6. David M. Berson
  7. Stephanie E. Palmer
  8. Wei Wei

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Abstract

Spatially distributed excitation and inhibition collectively shape a visual neuron’s receptive field (RF) properties. In the direction-selective circuit of the mammalian retina, the role of strong null-direction inhibition of On-Off direction-selective ganglion cells (ON-OFF DSGCs) on their direction selectivity is well-studied. However, how excitatory inputs influence the On-Off DSGC’s visual response is underexplored. Here, we report that On-Off DSGCs have a spatially displaced glutamatergic receptive field along their preferred-null motion axis. This displaced receptive field contributes to DSGC null-direction spiking during interrupted motion trajectories. Theoretical analyses indicate that population responses during interrupted motion may help populations of On-Off DSGCs signal the spatial location of moving objects in complex, naturalistic visual environments. Our study highlights that the direction-selective circuit exploits separate sets of mechanisms under different stimulus conditions, and these mechanisms may help encode multiple visual features.

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  1. eLife

    ###Reviewer #3:

    This very interesting manuscript further describes the receptive field structure of ON-OFF retinal direction selective ganglion cells. The authors demonstrate that spot light stimuli flashed at positions that do not correspond with dendritic processes of the recorded DSGC evoke strong excitatory responses that are most powerful on the preferred side of the (moving bar determined) receptive field. The authors go on to show that small light stimuli flashed in the dendritically sampled area of visual space are also non-uniform, and maximal on the preferred side. The authors data are in line with previous reports of a nondirectional zone at the periphery of the dendritic tree of DSGCs. The experimental approaches taken by the authors seem sound. I was concerned by the obviously different kinetics of the flash response recorded under control and GABAA/nAChR antagonists in Figure 1 D, is this a consistent finding, what are the authors thoughts on the unusual shape of the current in Figure 1 D (lower, red trace)? As indicated in the discussion the authors have not investigated the mechanisms underlying this asymmetry, other than dismissing structural determinants (dendritic tree asymmetry, investigation of existing EM volume). This to my mind is a vital component missing from the manuscript. The authors however do go on to describe using elegant light stimulus patterns and modelling some of the potential emergent properties of this behaviour. In this reviewer's mind, I am left puzzled and wanting to understand the cellular basis of the behaviour the authors have identified.

  2. eLife

    ###Reviewer #2:

    In this research, Ding and colleagues present evidence that the excitatory input to OO DS RGCs from bipolar cells is strongly asymmetric, with strong inputs occurring on the side opposite from the SAC inhibition. They performed careful studies to show that this was not due to spatial asymmetry in the DSGC morphology nor to ribbon synapse density. Using 'interrupted motion' stimuli, which are effectively local directional stimuli, they show that this asymmetry leads to a non-directional response on one side of the cell's RF. Last, they create a model to show that such firing patterns could be used to improve localization of edge position under the specific conditions of an edge emerging from behind an occlusion.

    The work showing the asymmetry appeared careful, thorough, and well-done. The second half of the paper dealing with the functional consequences of this asymmetry left me with a few questions:

    1. Throughout the paper, several experiments showed no changes when a mix of receptor antagonists was added to exclude SAC inhibition as the origin of these effects. But I did not find a positive control, showing that these antagonists had the desired effect. Later, in Figures 5CD, the remaining effect after application of these antagonists was cited as evidence that the excitational asymmetry was responsible for the effect; that interpretation is only valid if the drugs truly kill all SAC input to the DSGC. What if the drugs were not 100% effective? Relatedly, in the experiments in 5CD, the measured responses all decrease with the antagonists, an effect that seems surprising and is not explained. Connecting the asymmetry in excitation to the interrupted motion is central to this paper, so it should have strong support.

    2. The measured functional results appear quite similar to results in Kuhn & Gollisch 2019, which is not cited in that context. That paper found that DSGCs responded to local contrast, not just motion, much like the results here, and suggested that oppositely tuned cells could be subtracted to eliminate this contaminating contrast signal or added to isolate the contrast signal. Here, the authors suggest a very similar use for these signals, albeit with a decoder of position and a focus on motion rather than contrast changes. (See line 528, where the authors suggest that this position-direction hypothesis is new. See also line 537: or could not be salient, if there's any kind of downstream opponent subtraction, as in primate MT.)

    3. The interrupted motion stimuli are more complex than standard motion stimuli, but it's not clear how ethological or naturalistic they really are. In particular, the occluder was the same contrast as the rest of the background, which seems like a very specific kind of occluded motion, and it's not clear how this would generalize when the occlude is the same or opposite contrast of the moving edge. Moreover, the existence of directed motion in these stimuli lead the authors to emphasize the motion on the 'preferred side', rather than just non-directional contrast changes, which seem as though they would also induce responses.

    4. The modeling/decoding aspect of this paper seems pretty speculative. It doesn't seem as though these cells are known to be involved in any kind of position encoding. The fact that they transmit information about contrast changes means they can enhance position-decoding, but many other RGCs could also (better?) serve this purpose. The optic-flow-field arrangement of these cells in the retina suggests just the opposite - that they appear likely to be used for optic flow detection, in which positional information is less relevant than the field structure.

    5. Last, I kept wondering how this offset excitatory input made the DSGCs look very similar to a classical Barlow-Levick model (though with DS inhibition). I believe a classical BL model would have many of the properties shown here, including the sensitivity to occluded ND motion on its 'preferred side'. Is there an advantage in the BL model formulation to having disjoint excitatory and inhibitory spatial inputs, rather than a broad excitatory field that overlaps with the delayed inhibition? If so, would such an advantage explain why this asymmetry might exist in these DSGCs, even with DS inhibition from the SACs? I guess I'm asking whether there is an advantage for general motion detection, rather than proposing a new role for these cells in localizing specific types of motion stimuli.

  3. eLife

    ###Reviewer #1:

    This paper describes a new finding about stimulus encoding in On-Off directionally selective ganglion cells. It is well established that these cells have spatially displaced inhibitory input from starburst amacrine cells, and that the spatial offset of inhibitory input contributes to the cells' selectivity for direction of motion. The work in this paper shows that the cells also have spatially offset excitatory input, and that this input can give rise to a non-directional response. Several functional roles are suggested for the non-directional response. I felt that the evidence for the non-directional response was strong, but that the connection to visual function was too preliminary.

    Functional importance:

    The paper emphasizes the possible functional importance of the non-directional motion signal; this is a focus of the discussion, and is highlighted in both the abstract and introduction. I found this part of the paper less complete and convincing than the experimentally-driven results. Several issues contribute to this. One is that the contribution to identifying the position of a moving object is fairly modest. Another is that the impact of the non-directional component on other stimulus properties - e.g. the accuracy with which motion direction is encoded - is not explored. A third is that the position of a moving object is almost certainly encoded by multiple ganglion cell types, and hence the modest improvement in position encoding in the DS cell population may make even less contribution when the entire ganglion cell population is considered. A complete investigation of coding in the ganglion cell population is clearly too much, but a more balanced and complete consideration of the benefits and drawbacks of the mechanism described would strengthen the paper considerably.

  4. eLife

    ##Preprint Review

    This preprint was reviewed using eLife’s Preprint Review service, which provides public peer reviews of manuscripts posted on bioRxiv for the benefit of the authors, readers, potential readers, and others interested in our assessment of the work. This review applies only to version 2 of the manuscript.

    ###Summary:

    The reviewers were in broad agreement that the findings were interesting and that the experiments were well executed and clear. The main concern is that the paper does not provide either a definitive mechanistic insight into why excitatory input is asymmetric, or a definitive functional argument about the importance of this asymmetry.

  5. Version published to 10.1101/2020.05.29.124461 on bioRxiv