Differential encoding of the visual field in the mouse retina:
The finding that RGCs can dynamically change their light responses with changes in the visual input led us to hypothesize that RGCs may also change their light responses with their location within the retina. Conventionally, RGCs belonging to the same subtype are expected to share the same light responses all over the retinal area to uniformly encode a specific visual property in the entire visual field. But the visual input is often non-homogenic. For example, a small animal like the mouse views the environment from close to the ground, so the upper visual field primarily detects the sky while the lower visual field primarily detects the ground. We studied one RGC subtype, the transient-Off-alpha RGC, and found that neurons belonging to this subtype change their light responses with retinal location, changing gradually along the ventral-dorsal axis. This change resulted from differential input from retinal interneurons called AII cells. Our findings suggest that retinal networks adjust to the prevailing visual image to enable optimized sampling of the visual scene.
Revealing the mechanisms allowing for dynamic changes in encoding properties of DS-RGCs:
DS-RGCs encode the direction of motion in the visual field: they respond strongly to an object moving in one (preferred) direction but not in the opposite direction. Extensive studies have shown that the asymmetric response is hardwired and relies on asymmetric inhibitory inputs from starburst amacrine cells (SACs). Yet, we previously found that DS-RGCs can reverse their directional preference following a short repetitive visual stimulation. What are the mechanisms that allow DS-RGCs to overcome their circuit anatomy and reverse their directional preference?
On-SACs, like many other neurons in the visual system display antagonistic center-surround receptive field organization: they depolarize in response to light increment in the center, but depolarize in response to light decrement in the surround receptive field. We found that repetitive visual stimulation eliminates SAC center response and enhances SAC surround response. This change in receptive field organization causes a shift in SAC response time which underlies reversal in DS-RGCs. Thus, we identified antagonistic center-surround mechanism for retinal direction selectivity.
Dopamine differentially affects retinal circuits to shape the retinal code:
Dopamine acts as a neuromodulator in the retina. Its concentrations change with the circadian rhythm, being high during the day and low during the night. This suggests that retinal neurons can dynamically change over time. Dopamine has long been reported to enhance antagonistic surrounds of RGCs, sharpening their receptive fields. Using MEA recordings we found that dopamine can either increase or decrease RGCs’ surround strength, depending on their subtype. For example, we found that dopamine enhances the center response of transient-Off-alpha RGCs, but has different, even opposing, effects on the two main pathways that underlie the surround response of the cells. Our findings demonstrate that dopamine affects RGC subtypes via distinct pathways, suggesting that response properties of RGCs are differentially modulated with the changing dopamine levels across the circadian rhythm.
Elucidate how histaminergic signaling from the brain affects visual processing in the retina:
We usually treat the retina as an autonomous neuronal tissue that processes the visual image and projects its output to the brain. Yet, more than a century ago, Ramon y Cajal showed that the retina is innervated by retinopetal axons coming from the brain. How such inputs affect retinal processing has remained unknown. We identified brain-to-retina projections of histaminergic neurons in the tuberomamillary nucleus (TMN) of the hypothalamus. We found that histamine application alters the spontaneous and light-evoked activity of various RGCs, including DS-RGCs which improve their ability to detect higher velocity motion. Such changes could improve vision when objects move fast across the visual field (e.g. while an animal is running), which fits with the known increase in histaminergic neurons’ activity during arousal. Our findings expose a previously unappreciated role for brain-to-retina projections in modulating retinal function, revealing a novel mechanism for retinal dynamic computing in which the processing of the visual information does not only change with the visual input, but also with the behavioral state of the animal.
