The flash electroretinogram (ERG) is a useful tool for assessing retinal function in both the laboratory and the clinic. It is a mass electrical potential that changes in a characteristic way in response to an increase in retinal illumination, and it can be recorded non-invasively using a corneal electrode. Recording non-invasively provides the opportunity for studying retinal function while maintaining an essentially normal physiological environment for the tissue. However, because it is a mass potential, the ERG represents the summed activity of all retinal cells. For specific information about retinal function, it is important to be able to separately analyse the contributions from the cells and circuits that combine to form the mass response.Much research on the flash ERG has focused on separating the various components of the response that correspond to different retinal cell types. As a result, it is well known that the initial waves of the dark-adapted (scotopic) ERG, the a-and b-waves, originate mainly from cells at early stages of retinal processing. Following an intense brief flash of light from darkness, the negative-going a-wave is generated by rod photocurrents (Penn & Hagins, 1969) and the positive-going b-wave by depolarizing bipolar-cell currents in combination with bipolar cell-dependent K + currents affecting Müller cells (Miller & Dowling, 1970;Stockton & Slaughter, 1989;Xu & Karwoski, 1994;Shiells & Falk, 1999;Robson & Frishman, 1995; for a review see Pugh et al. 1998). For weaker flashes, the a-wave is too small to be seen in the record, and the dominant component of the ERG is the b-wave.For very weak flashes from darkness, in several mammals, e.g. cats, monkeys, humans, and rats, a small post-
A cone photoreceptor releases glutamate at ribbons located atop narrow membrane invaginations that empty onto a terminal base. The unique shape of the cone terminal suggests that there are two transmitter microenvironments: within invaginations, where concentrations are high and exposures are brief; and at the base, where concentrations are low and exposure is smoothed by diffusion. Using multicell voltage-clamp recording, we show that different subtypes of Off bipolar cells sample transmitter in two microenvironments. The dendrites of an AMPA receptor-containing cell insert into invaginations and sense rapid fluctuations in glutamate concentration that can lead to transient responses. The dendrites of kainate receptor-containing cells make basal contacts and respond to a smoothed flow of glutamate that produces sustained responses. Signaling at the cone to Off bipolar cell synapse illustrates how transmitter spillover and synapse architecture can combine to produce distinct signals in postsynaptic neurons.
The electroretinogram (ERG) of anaesthetised dark‐adapted macaque monkeys was recorded in response to ganzfeld stimulation and rod‐ and cone‐driven receptoral and postreceptoral components were separated and modelled. The test stimuli were brief (< 4.1 ms) flashes. The cone‐driven component was isolated by delivering the stimulus shortly after a rod‐saturating background had been extinguished. The rod‐driven component was derived by subtracting the cone‐driven component from the mixed rod–cone ERG. The initial part of the leading edge of the rod‐driven a‐wave scaled linearly with stimulus energy when energy was sufficiently low and, for times less than about 12 ms after the stimulus, it was well described by a linear model incorporating a distributed delay and three cascaded low‐pass filter elements. Addition of a simple static saturating non‐linearity with a characteristic intermediate between a hyperbolic and an exponential function was sufficient to extend application of the model to most of the leading edge of the saturated responses to high energy stimuli. It was not necessary to assume involvement of any other non‐linearity or that any significant low‐pass filter followed the non‐linear stage of the model. A negative inner‐retinal component contributed to the later part of the rod‐driven a‐wave. After suppressing this component by blocking ionotropic glutamate receptors, the entire a‐wave up to the time of the first zero‐crossing scaled with stimulus energy and was well described by summing the response of the rod model with that of a model describing the leading edge of the rod‐bipolar cell response. The negative inner‐retinal component essentially cancelled the early part of the rod‐bipolar cell component and, for stimuli of moderate energy, made it appear that the photoreceptor current was the only significant component of the leading edge of the a‐wave. The leading edge of the cone‐driven a‐wave included a slow phase that continued up to the peak, and was reduced in amplitude either by a rod‐suppressing background or by the glutamate analogue, cis‐piperidine‐2,3‐dicarboxylic acid (PDA). Thus the slow phase represents a postreceptoral component present in addition to a fast component of the a‐wave generated by the cones themselves. At high stimulus energies, it appeared less than 5 ms after the stimulus. The leading edge of the cone‐driven a‐wave was adequately modelled as the sum of the output of a cone photoreceptor model similar to that for rods and a postreceptoral signal obtained by a single integration of the cone output. In addition, the output of the static non‐linear stage in the cone model was subject to a low‐pass filter with a time constant of no more than 1 ms. In conclusion, postreceptoral components must be taken into account when interpreting the leading edge of the rod‐ and cone‐driven a‐waves of the dark‐adapted ERG.
Microspectrophotometry studies show that zebrafish (Danio rerio) possess four cone photopigments. The purpose of this study was to determine the cone contributions to the zebrafish photopic increment threshold spectral-sensitivity function. Electroretinogram (ERG) b-wave responses to monochromatic lights presented on a broadband or chromatic background were obtained. It was found that under the broadband background condition, the zebrafish spectral-sensitivity function showed several peaks that were narrower in sensitivity compared to the cone spectra. The spectral-sensitivity function was modeled with L − M and M − S opponent interactions and nonopponent S- and U-cone mechanisms. Using chromatic adaptation designed to suppress the contribution of the S-cones, a strong U-cone contribution to the spectral-sensitivity function was revealed, and the contributions of the S-cones to the M − S mechanism were reduced. These results show that the b-wave component of the ERG receives input from all four cone types and appears to reflect color opponent mechanisms. Thus, zebrafish may possess the fundamental properties necessary for color vision.
Anatomical studies of the developing zebrafish retina have shown that rods approach maturity at about 15 days postfertilization (dpf). Past work has examined the photopic spectral sensitivity function of the developing zebrafish, but not spectral sensitivity under darkadapted conditions. This study examined rod contributions to the dark-adapted spectral sensitivity function of the ERG b-wave component in developing zebrafish. ERG responses to stimuli of various wavelengths and irradiances were obtained from dark-adapted fish at 6-8, 13-15, 21-24, and 27-29 dpf. The results show that dark-adapted spectral sensitivity varied with age. Spectral sensitivity functions of the 6-8 and 13-15 dpf groups appeared to be cone dominated and contained little or no rod contributions. Spectral sensitivity functions of the 21-24 and 27-29 dpf groups appeared to have both rod and cone contributions. Even at the oldest age group tested, the darkadapted spectral sensitivity function did not match the adult function. Thus, consistent with anatomical findings, the rod contributions to the ERG spectral sensitivity function appear to develop with age; however, these contributions are still not adult-like by 29 dpf, which is contrary to anatomical work. These results illustrate that the zebrafish is an excellent model for visual development.
Cone bipolar cells of the vertebrate retina connect photoreceptors with ganglion cells to mediate photopic vision. Despite this important role, the mechanisms that regulate cone bipolar cell differentiation are poorly understood. VSX1 is a CVC domain homeoprotein specifically expressed in cone bipolar cells. To determine the function of VSX1, we generated Vsx1 mutant mice and found that Vsx1 mutant retinal cells form but do not differentiate a mature cone bipolar cell phenotype. Electrophysiological studies demonstrated that Vsx1 mutant mice have defects in their cone visual pathway, whereas the rod visual pathway was unaffected. Thus, Vsx1 is required for cone bipolar cell differentiation and regulates photopic vision perception.
The zebrafish has become an important vertebrate model in developmental neuroscience because it is a useful model for embryology, developmental biology, and genetic analysis. The similarities of its visual system to that of other vertebrates also make this animal a valuable model in vision science. The anatomical, physiological, and behavioral components of zebrafish visual processing have been studied in adult and in developing zebrafish. Its retinal anatomy continues to develop following hatching, providing an opportunity to correlate the development of retinal structure with visual physiology and behavior. In addition, a number of genetic mutations have been developed which are used to examine the contributions of genetics to visual development and function. This article will provide an overview of studies of zebrafish anatomical, physiological and behavioral processing, and the effects if genetic and environmental manipulations on visual development.
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