Adaptation to Background Light Enables Contrast Coding at Rod Bipolar Cell Synapses

Ke, Jiang Bin; Wang, Yanbin V.; Borghuis, Bart G.; Cembrowski, Mark S.; Riecke, Hermann; Kath, William L.; Demb, Jonathan B.; Singer, Joshua H.

doi:10.1016/j.neuron.2013.10.054

Cited by 78 publications

(101 citation statements)

References 51 publications

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“…RGC temporal tuning likely reflects the relative contribution of these different circuits. The RBC-AIIAC circuit is an example of a mixed rod-cone circuit and it would have slower temporal kinetics than cone circuits (15,27). Weakening of the RBC-AIIAC synapse could increase the relative contribution of faster circuits, leading to an acceleration of the RGC temporal tuning.…”

Section: Discussionmentioning

confidence: 99%

Elevated IOP alters the space–time profiles in the center and surround of both ON and OFF RGCs in mouse

Sabharwal

Seilheimer

Tao

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Glaucoma is a leading cause of blindness worldwide, and is characterized by progressive retinal ganglion cell (RGC) death. An experimental model of glaucoma has been established by elevating the intraocular pressure (IOP) via microbead occlusion of ocular fluid outflow in mice. Studies in this model have found visual dysfunction that varied with adaptational state, occurred before anatomical changes, and affected OFF RGCs more than ON RGCs. These results indicate subtle alterations in the underlying retinal circuitry that could help identify disease before irreversible RGC changes. Therefore, we looked at how RGC function was altered with elevated IOP under both photopic and scotopic conditions. We first found that responses to light offset are diminished with IOP elevation along with a concomitant decrease in receptive field center size for OFF RGCs. In addition, the antagonistic surround strength and size was reduced in ON RGCs. Furthermore, elevation of IOP significantly accelerated the photopic temporal tuning of RGC center responses in both ON and OFF RGCs. We found that some of the IOP-induced functional changes to OFF RGCs relied on ON cross-over pathways, indicating dysfunction in inner retinal circuitry. Overall, these results suggest that IOP alters multiple functions in the retina depending on the adaptational state. They provide a basis for designing multiple functional tests for early detection of glaucoma and for circuit-specific therapeutic targets in treatment of this blinding disease.retinal ganglion cell | glaucoma | IOP | receptive field | multielectrode array G laucoma is one of the leading causes of blindness worldwide (1). It is a progressive disease and most patients are only identified after an irreversible visual deficit is already present (2). Diagnosing patients with subtle functional deficits that occur before this irreversible visual deficit will significantly improve a patient's ability to preserve normal vision.Elevated intraocular pressure (IOP) is a critical risk factor for glaucoma and the central focus of glaucoma treatment (3, 4). Mouse models of glaucoma are also dependent on raising IOP. One method to elevate IOP is to inject microbeads into the eye to block normal fluid outflow (5). Previous studies on this mouse model have found that high IOP causes changes in retinal ganglion cell (RGC) anatomy and eventual cell death leading to irreversible vision loss as seen in glaucoma (5-7). Before these changes, functional properties, such as RGC light sensitivity and photopic receptive field (RF) center size, are altered (8-12). A better understanding of these functional changes may help to detect human disease before irreversible cell death.In addition to RGC changes, behavioral tests have found that spatiotemporal tuning under photopic and scotopic conditions is altered (10). These behavioral studies suggest alteration in additional functional properties related to spatiotemporal tuning, such as scotopic receptive field size, temporal tuning, and the antagonistic surround.To det...

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Section: Discussionmentioning

confidence: 99%

Elevated IOP alters the space–time profiles in the center and surround of both ON and OFF RGCs in mouse

Sabharwal

Seilheimer

Tao

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…Therefore, the difference is in the extent of S-cone versus M-cone activation and their downstream bipolar cells. Although chromatic differences in targeting of different bipolar cell types has been explored in the adult mouse (Haverkamp et al, 2005;Breuninger et al, 2011;Wang et al, 2011;Euler et al, 2014), the specificity of wiring during development is unknown. Whether activity plays a role in the establishment of these synapses in the later maturing OFF pathway similar to what has been demonstrated for the ON pathway (Morgan et al, 2011;Dunn et al, 2013;Johnson and Kerschensteiner, 2014) remains to be determined.…”

Section: Late Development Of Off S-cone Pathwaymentioning

confidence: 99%

“…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).…”

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confidence: 99%

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

et al. 2016

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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...

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“…primed vesicles for release at the presynaptic membrane (Heidelberger et al, 2005;Snellman et al, 2011). Recent studies have shown that the interplay of vesicle release and replenishment at the ribbon are important in encoding luminance and contrast by cones (Jackman et al, 2009;Babai et al, 2010) and rod BCs (RBCs; Oesch and Diamond, 2011;Ke et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Calmodulin enhances ribbon replenishment and shapes filtering of synaptic transmission by cone photoreceptors

Hook¹,

Parmelee²,

Chen³

et al. 2014

J Cell Biol

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At the first synapse in the vertebrate visual pathway, light-evoked changes in photoreceptor membrane potential alter the rate of glutamate release onto second-order retinal neurons. This process depends on the synaptic ribbon, a specialized structure found at various sensory synapses, to provide a supply of primed vesicles for release. Calcium (Ca 2+ ) accelerates the replenishment of vesicles at cone ribbon synapses, but the mechanisms underlying this acceleration and its functional implications for vision are unknown. We studied vesicle replenishment using paired whole-cell recordings of cones and postsynaptic neurons in tiger salamander retinas and found that it involves two kinetic mechanisms, the faster of which was diminished by calmodulin (CaM) inhibitors. We developed an analytical model that can be applied to both conventional and ribbon synapses and showed that vesicle resupply is limited by a simple time constant,  = 1/(Ds), where D is the vesicle diffusion coefficient,  is the vesicle diameter,  is the vesicle density, and s is the probability of vesicle attachment. The combination of electrophysiological measurements, modeling, and total internal reflection fluorescence microscopy of single synaptic vesicles suggested that CaM speeds replenishment by enhancing vesicle attachment to the ribbon. Using electroretinogram and whole-cell recordings of light responses, we found that enhanced replenishment improves the ability of cone synapses to signal darkness after brief flashes of light and enhances the amplitude of responses to higherfrequency stimuli. By accelerating the resupply of vesicles to the ribbon, CaM extends the temporal range of synaptic transmission, allowing cones to transmit higher-frequency visual information to downstream neurons. Thus, the ability of the visual system to encode time-varying stimuli is shaped by the dynamics of vesicle replenishment at photoreceptor synaptic ribbons.

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Adaptation to Background Light Enables Contrast Coding at Rod Bipolar Cell Synapses

Cited by 78 publications

References 51 publications

Elevated IOP alters the space–time profiles in the center and surround of both ON and OFF RGCs in mouse

Elevated IOP alters the space–time profiles in the center and surround of both ON and OFF RGCs in mouse

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

Calmodulin enhances ribbon replenishment and shapes filtering of synaptic transmission by cone photoreceptors

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