Contributions of Rod and Cone Pathways to Retinal Direction Selectivity Through Development

Abstract

Direction selectivity is a robust computation across a broad stimulus space that is mediated by activity of both rod and cone photoreceptors through the ON and OFF pathways. However, rods, S-cones, and M-cones activate the ON and OFF circuits via distinct pathways and the relative contribution of each to direction selectivity is unknown. Using a variety of stimulation paradigms, pharmacological agents, and knockout mice that lack rod transduction, we found that inputs from the ON pathway were critical for strong direction-selective (DS) tuning in the OFF pathway. For UV light stimulation, the ON pathway inputs to the OFF pathway originated with rod signaling, whereas for visible stimulation, the ON pathway inputs to the OFF pathway originated with both rod and M-cone signaling. Whole-cell voltageclamp recordings revealed that blocking the ON pathway reduced directional tuning in the OFF pathway via a reduction in null-side inhibition, which is provided by OFF starburst amacrine cells (SACs). Consistent with this, our recordings from OFF SACs confirmed that signals originating in the ON pathway contribute to their excitation. Finally, we observed that, for UV stimulation, ON contributions to OFF DS tuning matured earlier than direct signaling via the OFF pathway. These data indicate that the retina uses multiple strategies for computing DS responses across different colors and stages of development.Key words: development; direction selectivity; direction selective ganglion cells; Gnat1; retina; rod/cone pathway IntroductionOne of the remarkable properties of the retina is its ability to encode visual features for both ON and OFF polarity in light intensities that vary across several orders of magnitude and spectral content. For example, direction-selective ganglion cells (DSGCs), which fire strongly when an object moves in the preferred direction (PD) and fire minimally when the object moves in the opposite (null) direction (ND) (Fig. 1B), show similar tuning across different light intensities (Hoggarth et al., 2015). Responses across light conditions are mediated by different classes of photoreceptors: rod photoreceptors are active at low light levels, whereas S-cone and M-cone photoreceptors become active at bright light levels. In the mouse retina, rod-mediated signaling also contributes to visual processing in intermediate and bright light conditions (Ke et al., 2014; Szikra et al., 2014; Vlasits et al., 2014;Grimes et al., 2015;Tikidji-Hamburyan et al., 2015; Joesch and Meister, 2016), indicating that a complex set of interactions between rod and cone pathways influence the encoding features of the retina.Cones and rods feed into circuits that are initially distinct in the outer retina, but then converge onto the same cell types in the inner retina (Fig. 1A). Cones synapse onto two major subtypes of cone bipolar cells (cBCs): ON cBCs that depolarize in response to increases in light and OFF cBCs that depolarize in response to deReceived Oct. 19, 2015; revised July 11, 2016; accepted July 28, 2016 Significa...

Visual experience instructs dendrite orientation but is not required for asymmetric wiring of the retinal direction selective circuit

“…Surprisingly, we observed no differences in the strength or orientation of DS tuning in any of the experimental groups (Figures 2b and 2c). Note, that OFF responses were less tuned at eye opening (Figure 2c), consistent with findings that OFF DS circuits mature later than ON circuits (Hoon et al, 2014;Rosa et al, 2016). Thus, we only analyzed ON spike tuning for P13/14.…”

Pan-retinal characterisation of Light Responses from Ganglion Cells in the Developing Mouse Retina

“…Such detailed classification is however not feasible in immature retinas. Indeed, the responses to light in a P13 retina are very immature shortly after eye opening (around P12) and it is literally impossible to cluster beyond basic types (ON, OFF and ON-OFF) and direction/orientation selective cells consistently through retina development 10 11 12 37 . An additional problem is that temporal parameters used to establish sustained or transient criteria are not robust enough in maturing RGCs, as we show in our study (see also Supplemental Fig.…”

Antagonistic center-surround mechanisms for direction selectivity in the retina

“…Polarity switch in On-SAC did not rely on changes in inhibitory surround circuits in the inner retina, but rather on opposed polarity activation of presynaptic On bipolar cells (Vlasits et al, 2014). This was suggested to result from loss of rod signaling, which takes part in the computation of motion direction (Rosa et al, 2016). Specifically, rods are saturated in response to the high-light levels RVS and no longer transduce light into electrical responses.…”