Sensitivity and dynamic range are two important characteristics of sensory receptors in the nervous system that define the physiological role of these cells. Rod cells in the retina of a mouse have the ability to detect very dim lights by closing cyclic-gated nucleotide channels. This extreme sensitivity would be impractical if the dynamic range on these cells was limited. Adaptation is a process by which the sensitivity of the transduction cascade is adjusted so cells can function within broader ranges of stimuli. Electrical recordings of circulating currents have been used to show that in the presence of steady background light, rods are desensitized so that saturation doesn't occur, and they remain responsive to increments and decrements of illumination. Furthermore, changes in calcium concentration have been proposed to mediate modulations of various molecules within the transduction pathways. In this project, we investigated the time course of desensitization and recovery in adaptation using suction electrode recording. We were able to show, desensitization at various ranges of adapting light, as manifested by the fact that reduction in sensitivity acceleration of recovery is already present at 500 ms. We also demonstrated that in recovery from adaptation, sensitivity of the rod returns back to its dark-adapted levels within 2 seconds. The persistence of adaptation in the form of acceleration of recovery was present with extremely dim lights and the time constant of its recovery to dark-adapted levels was dependent on the intensity of the background light.

Lamprey are cyclostomes, which diverged from jawed vertebrates (fishes, amphibians, mammals) in the Cambrian perhaps 500 Mya. Using single-cell measurements with suction recording from the photoreceptors of adult�Petromyzon marinus�we first show that this primitive vertebrate has a duplex retina: rods respond to single photons, have a longer integration time, and are 80 times more sensitive than cones, much as in other vertebrates. We then demonstrate that responses to maintained steps of light decay as in other vertebrates and flash responses superimposed on steady backgrounds show decreases in sensitivity and changes in waveform in both rods and cones, also typical of other vertebrates. Backgrounds produce a decrease in maximum flash-response amplitude and an increase in the flash intensity necessary to produce a detectable response, with characteristic shifts of response-intensity curves along the intensity axis. Increasing background light had little effect on response onset but monotonically increased the rate of response decay. Sensitivity as a function of background intensity decreased by Weber’s Law in both rods and cones; rods show incremental saturation, and cones begin to adapt near the intensity at which rod saturation occurs. Bright bleaching light produces an equivalent background, with opsin in rods 7.5 x 10-6�times as effective in stimulating the cascade as Rh* (2 x 10-5�in mouse rods). The decreases in sensitivity and acceleration of response decay in stably bleached photoreceptors can be nearly completely reversed with exogenous 11-cis�retinal.

We then used mice to demonstrate that in wild-type animals background lights decrease the sensitivity of the rod and accelerate the kinetics of the response, and these processes occur rapidly within 250ms after presentation of the background. We also recorded the dark current from recoverin-knockout photoreceptors and did not detect any changes in flash sensitivity. However, responses to steps of light were significantly desensitized and the rate of reduction in sensitivity is much faster when recoverin is eliminated compared to wild-type rods. The waveform of the response however, appears to be independent of the background intensity in recoverin-knock out animals.

Unlike rods which mediate low-light/night vision, cones which mediate day-vision never saturate despite exposure to intense, ambient light. A contributing explanation is a M�ller cell-mediated visual cycle, found in mammalian models, that continually regenerates photopigment in cones (Wang et al., 2011). Given our knowledge of the “camera” eye (Lamb et al., 2007), we wanted to know if this cone-specific visual cycle was also highly conserved in vertebrates prompting the use of sea lamprey, an ideal model for evolutionary study. Using ERG recordings, we found no significant regaining of response sensitivity in isolated retinas, indicative of pigment regeneration, after a substantial bleaching light exposure. These results confirm the absence of a cone-specific visual cycle in sea lamprey and suggest that this pathway had arisen after the divergence of jawed and jawless vertebrates ~500 mya.

Humans rely heavily on vision to navigate and perform complex tasks, making it a crucial sensory modality. However, the mechanisms underlying the emergence of this modality are not yet fully understood. Thus, understanding the origins of the visual system is a critical goal of neuroscience, as it can help define poorly understood neural circuitry. This project proposes a descriptive investigation to determine the molecular and evolutionary underpinnings of vision formation, specifically focusing on cell-type mapping and region-specific gene expression in basal vertebrate lamprey species. By localizing key regulatory genes and identifying the cell types of our vertebrate ancestors, we can elucidate the developmental processes and functional mechanisms of vision, ultimately providing an evolutionary roadmap of retinal vision. This investigation significantly enhances the existing cellular taxonomy of retinal formation and reveals components of visual circuits that were prevalent even in the most primitive vertebrates.