Directionally tuned signalling in starburst amacrine cell (SAC) dendrites lies at the heart of the circuit that detects the direction of moving stimuli in the mammalian retina. The relative contributions of intrinsic cellular properties and network connectivity to SAC direction selectivity remain unclear. Here we present a detailed connectomic reconstruction of SAC circuitry in mouse retina and describe two previously unknown features of synapse distributions along SAC dendrites: input and output synapses are segregated, with inputs restricted to proximal dendrites; and the distribution of inhibitory inputs is fundamentally different from that observed in rabbit retina. An anatomically constrained SAC network model suggests that SAC–SAC wiring differences between mouse and rabbit retina underlie distinct contributions of synaptic inhibition to velocity and contrast tuning and receptive field structure. In particular, the model indicates that mouse connectivity enables SACs to encode lower linear velocities that account for smaller eye diameter, thereby conserving angular velocity tuning. These predictions are confirmed with calcium imaging of mouse SAC dendrites responding to directional stimuli.
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We thank W. Denk for supporting the collection of the serial block-face scanning electron microscopy data in his laboratory. This work was supported by NIH grants EY016607 and EY022070 (RGS), by the NINDS Intramural Research Program (NS003145; J.S.D.) and (NS003133; K.L.B.), the Max-Planck Society (K.L.B.), and the Pew Charitable Trusts (K.L.B.).
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Extended data figures and tables
a, Conventionally stained serial block-face scanning electron microscopy volume of a mouse retina. b, Reconstructed ON-OFF DSGC. c–e, A second reconstructed ON and OFF SAC with annotated synapses locations. f, Annotation of the radial distribution of input and output synapses to and from approximately one-half of an OFF SAC dendritic arbor in rabbit retina. Data analysed from fig. 15 in ref. 2.
a, Types 1/2 and types 3/4 separated by IPL depth. b, Types 1 and 2 separate by stratification width and axonal arborization area (convex hull). c, Types 3a, 3b and 4 separate by stratification depth and axonal arborization area. d, Mosaic patterns and stratification profiles of OFF bipolar cells. e, The number of synapses (mean ± s.d.) each bipolar cell, by type, formed with each SAC. f, Location of bipolar cell synapses onto a second OFF SAC, colour-coded by bipolar cell type. g, The IPL depth of each synapse versus the radial distance relative to the soma.
a, Type 5 and type 7 biploar cells separated by IPL depth. b, Types 5o (outer), 5t (thick) and 5i (inner) further subdivide based on IPL depth and stratification width. c, Mosaic patterns and stratification profiles of ON bipolar cells. d, Summary of the number of synapses (mean ± s.d.) each bipolar cell, by type, formed with each SAC. e, Location of bipolar cell synapses onto a second ON SAC, colour-coded by bipolar cell type. f, The IPL depth of each synapse versus the radial distance relative to the soma.
a, b, SACs presynaptic to the second pair of mouse SACs colour-coded by absolute orientation. c, d, Wide-field amacrine cells presynaptic to SACs. e, Narrow-field amacrine cells presynaptic to ON SACs.
a, Schematic of the relative angle measurement: parallel wiring = 0°, anti-parallel wiring = 180°. b, Locations of SAC input synapses colour-coded by relative angle. Grey locations indicate AC synapses that were not analysed. c, Cumulative distributions of the relative angles between each presynaptic and postsynaptic OFF SAC dendrite for synapses (black) and proximities (grey). Dashed line indicates a uniform distribution. d, Relative angle for each synapse was uncorrelated with the radial distance from the postsynaptic somas (r = 0.07, P = 0.16). Scale bar, 50 μm.
a, Percentage of output synapses formed with different postsynaptic cell types, colour-coded by postsynaptic cell class: ganglion cells (GC) (blue), SACs (red), bipolar cells (BC) (cyan), and wide-field amacrine cells (WAC) (green). b, Locations of 83 annotatedoutput synapses on 1 ON SAC dendrite fragment. c, Locations of 110 annotated output synapses on 2 OFF SAC dendrite fragments. Scale bar, 50 μm.
a, Dendrite diameters sampled from an ON SAC (grey) and an OFF SAC (black) at different radial distances from their respective somas. b, Single SAC morphology used in all simulations. c, Somatic voltage clamp simulation showed poor space clamp of even proximal dendrites. Voltage traces measured at a different distances (20–150 μm) from the soma. d, Somatic (solid line) and distal dendrite (dashed line) voltage time series in response to an annulus moving centrifugally or centripetally. The addition of active conductances to SAC dendrites (see Extended Data Table 1) rendered somatic voltage recordings directionally selective for centrifugal compared to centripetal stimulation, consistent with electrophysiological measurements. Scale bar, 50 μm.
a, Schematic of the difference in axial diameters and subtended angle on the retina of rabbit and mouse eyes. b, Linear velocity tuning curves from rabbit and mouse ON–OFF DSGCs. c, Angular velocity tuning curves from rabbit and mouse ON–OFF DSGCs. Data analysed from fig. 2F of ref. 31 and fig. 1D of ref. 32.
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Ding, H., Smith, R., Poleg-Polsky, A. et al. Species-specific wiring for direction selectivity in the mammalian retina. Nature 535, 105–110 (2016). https://doi.org/10.1038/nature18609
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