The spatial structure of a nonlinear receptive field

Abstract

Understanding a sensory system implies the ability to predict responses to a variety of inputs from a common model. In the retina, this includes predicting how the integration of signals across visual space shapes the outputs of retinal ganglion cells. Existing models of this process generalize poorly to predict responses to new stimuli. This failure arises in part from properties of the ganglion cell response that are not well captured by standard receptive-field mapping techniques: nonlinear spatial integration and fine-scale heterogeneities in spatial sampling. Here we characterize a ganglion cell's spatial receptive field using a mechanistic model based on measurements of the physiological properties and connectivity of only the primary excitatory circuitry of the retina. The resulting simplified circuit model successfully predicts ganglion-cell responses to a variety of spatial patterns and thus provides a direct correspondence between circuit connectivity and retinal output.

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Figure 1: Receptive fields of On alpha-like RGCs have heterogeneous structure and nonlinear subunits.
Figure 2: Nonlinear and heterogeneous receptive-field properties cause unique responses to stimuli with fine spatial structure.
Figure 3: Excitatory inputs and spike responses have similar sensitivity to rotation.
Figure 4: Type 6 bipolar cells contact the majority of excitatory postsynaptic sites on the On alpha-like RGC.
Figure 5: Nonlinear spatial interactions in the receptive field are aligned to the locations of type 6 bipolar cells.
Figure 6: Construction of the bipolar cell weight map from anatomical measurements.
Figure 7: A predictive model of RGC responses to two-dimensional patterns of light.
Figure 8: Tests of the predictive power of simplified receptive-field models.

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Acknowledgements

We thank D. Perkel, G. Field, M. Berry and W. Bair for helpful comments on the manuscript. This research was made possible by support from the US National Institutes of Health (EY11850 to F.R., EY10699 and EY017101 to R.O.W. and the Vision Core Grant EY 01730), the Howard Hughes Medical Institute (F.R.) and the Helen Hay Whitney Foundation (G.W.S.).

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Contributions

G.W.S. performed ganglion cell recordings, analysis and designed receptive-field models. H.O. performed imaging experiments and analyses (Figs. 4 and 6). F.A.D. performed bipolar cell recordings (Fig. 7b). J.L.M. and D.K. performed imaging experiments analyzed in Figure 6. G.W.S., R.O.W. and F.R. conceived of experiments and analyses. G.W.S., H.O., F.A.D., R.O.W. and F.R. wrote the paper.

Corresponding author

Correspondence to Gregory W Schwartz.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6, Supplementary Tables 1–3, Supplementary Discussion (PDF 3773 kb)

Supplementary Movie 1

Identifying appositions of PSD95 puncta with type 6 bipolar axon terminals. The dendritic segment shown in Figure 4c–e is zoomed in and rotated in three dimensions to demonstrate the identification of appositions with type 6 bipolar axon terminals. PSD95-CFP puncta, tdTomato filled alpha-like On RGC dendrites, On bipolar axons labeled by YFP and Syt2 immunoreactivity are shown in green, blue, red and white, respectively. The first set of flashing white dots represent all the identified PSD95 puncta and the second set show those apposed to On bipolar axon terminals. The red flashing dots represent PSD95 puncta classified as apposed to type 6 bipolar cells. (MOV 17179 kb)

Supplementary Movie 2

Identifying appositions of PSD95 puncta with type 7 bipolar axon terminals. The identification of the apposition of PSD95 puncta with type 7 bipolar cells is demonstrated in three dimensions in the same way as in Supplementary Movie 1 using the dendritic segment enlarged in Figure 4i,j. PSD95-CFP puncta, tdTomato filled alpha-like On RGC dendrites, type 7 bipolar axons labeled by GFP are shown in green, blue and red, respectively. The first set of flashing white dots represents all the identified PSD95 puncta and the second set represents those apposed to type 7 bipolar cells. (MOV 15646 kb)

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Schwartz, G., Okawa, H., Dunn, F. et al. The spatial structure of a nonlinear receptive field. Nat Neurosci 15, 1572–1580 (2012). https://doi.org/10.1038/nn.3225

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