Nonlinearities in retinal bipolar cells shape the encoding of artificial and natural stimuli

The retina dissects the visual scene into parallel feature channels, and bipolar cells are speculated to play a key role in this signal separation. Yet, bipolar cells are traditionally viewed as simple, linear neurons. Here, using the salamander retina, we investigated the hypothesis of linear signal processing in bipolar cells by intracellularly recording their voltage signals under artificial and natural visual stimuli. We observed nonlinear representation of contrast and, unexpectedly, also nonlinear spatial integration in a sizable fraction of bipolar cells. Furthermore, linear receptive field models fail to describe responses of nonlinear bipolar cells to spatially structured artificial and natural stimuli. The nonlinear properties occur in the receptive field center and may be cell-type specific, with stronger effects in transient than sustained bipolar cells. Thus, our data suggest that nonlinear signal pooling starts earlier than previously thought, that is, before signal integration in bipolar cells.

Receptive field center-surround interactions mediate context-dependent spatial contrast encoding in the retina

Antagonistic receptive field surrounds are a near-universal property of early sensory processing. A key assumption in many models for retinal ganglion cell encoding is that receptive field surrounds are added only to the fully formed center signal. But anatomical and functional observations indicate that surrounds are added before the summation of signals across receptive field subunits that creates the center. Here, we show that this receptive field architecture has an important consequence for spatial contrast encoding in the macaque monkey retina: the surround can control sensitivity to fine spatial structure by changing the way the center integrates visual information over space. The impact of the surround is particularly prominent when center and surround signals are correlated, as they are in natural stimuli. This effect of the surround differs substantially from classic center-surround models and raises the possibility that the surround plays unappreciated roles in shaping ganglion cell sensitivity to natural inputs.

Receptive field center-surround interactions mediate context-dependent spatial contrast encoding in the retina

SummaryAntagonistic receptive field surrounds are a near-universal property of early sensory processing. A key assumption in many models for retinal ganglion cell encoding is that receptive field surrounds are added only to the fully formed center signal. But anatomical and functional observations indicate that surrounds are added before the summation of signals across receptive field subunits that creates the center. Here, we show that this receptive field architecture has an important consequence for spatial contrast encoding: the surround can control sensitivity to fine spatial structure by changing the way the center integrates visual information over space. The impact of the surround is particularly prominent when center and surround signals are correlated, as they are in natural stimuli. This role of the surround differs substantially from classic center-surround models and raises the possibility that the surround plays unappreciated roles in shaping ganglion cell sensitivity to natural inputs.

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

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.

Distinct synaptic mechanisms create parallel S-ON and S-OFF color opponent pathways in the primate retina

Anatomical and physiological approaches are beginning to reveal the synaptic origins of parallel ON- and OFF-pathway retinal circuits for the transmission of short (S-) wavelength sensitive cone signals in the primate retina. Anatomical data suggest that synaptic output from S-cones is largely segregated; central elements of synaptic triads arise almost exclusively from the “blue-cone” bipolar cell, a presumed ON bipolar, whereas triad-associated contacts derive primarily from the “flat” midget bipolar cell, a hyperpolarizing, OFF bipolar. Similarly, horizontal cell connectivity is also segregated, with only the H2 cell-type receiving numerous contacts from S-cones. Negative feedback from long (L-) and middle (M-) wavelength sensitive cones via the H2 horizontal cells elicits an antagonistic surround in S-cones demonstrating that S versus L + M or “blue-yellow” opponency is first established in the S-cone. However, the S-cone output utilizes distinct synaptic mechanisms to create color opponency at the ganglion cell level. The blue-cone bipolar cell is presynaptic to the small bistratified, “blue-ON” ganglion cell. S versus L + M cone opponency arises postsynaptically by converging S-ON and LM-OFF excitatory bipolar inputs to the ganglion cell’s bistratified dendritic tree. The common L + M cone surrounds of the parallel S-ON and LM-OFF cone bipolar inputs appear to cancel resulting in “blue-yellow” antagonism without center-surround spatial opponency. By contrast, in midget ganglion cells, opponency arises by the differential weighting of cone inputs to the receptive field center versus surround. In the macula, the “private-line” connection from a midget ganglion cell to a single cone predicts that S versus L + M opponency is transmitted from the S-cone to the S-OFF midget bipolar and ganglion cell. Beyond the macula, OFF-midget ganglion cell dendritic trees enlarge and collect additional input from multiple L and M cones. Thus S-OFF opponency via the midget pathway would be expected to become more complex in the near retinal periphery as L and/or M and S cone inputs sum to the receptive field center. An important goal for further investigation will be to explore the hypothesis that distinct bistratified S-ON versus midget S-OFF retinal circuits are the substrates for human psychophysical detection mechanisms attributed to S-ON versus S-OFF perceptual channels.

Receptive field center size decreases and firing properties mature in ON and OFF retinal ganglion cells after eye opening in the mouse

Development of the mammalian visual system is not complete at birth but continues postnatally well after eye opening. Although numerous studies have revealed changes in the development of the thalamus and visual cortex during this time, less is known about the development of response properties of retinal ganglion cells (RGCs). Here, we mapped functional receptive fields of mouse RGCs using a Gaussian white noise checkerboard stimulus and a multielectrode array to record from retinas at eye opening, 3 days later, and 4 wk after birth, when visual responses are essentially mature. Over this time, the receptive field center size of ON and OFF RGC populations decreased. The average receptive field center size of ON RGCs was larger than that of OFF RGCs at eye opening, but they decreased to the same size in the adult. Firing properties were also immature at eye opening. RGCs had longer latencies, lower frequencies of firing, and lower sensitivity than in the adult. Hence, the dramatic maturation of the visual system during the first weeks of visual experience includes the retina.