(Exam 2) merge
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A small spot of light centered on a photoreceptor supplying input to the center of the ganglion cell's receptive field produces a strong hyperpolarizing response in the photoreceptor
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A three-neuron chain—photoreceptor cell to bipolar cell to ganglion cell—is the most direct path of information flow from photoreceptors to the optic nerve
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Absorption of light by the photopigment in the outer segment of the photoreceptors initiates a cascade of events that changes the membrane potential of the receptor, and therefore the amount of neurotransmitter released by the photoreceptor terminals; this process is called phototransduction
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Absorption of light by the photoreceptor reduces the concentration of cGMP in the outer segment, leading in turn to a closure of the cGMP-gated channels in the outer segment membrane and, consequently, a reduction in the inward flow of Na+ and Ca2+
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Activated rhodopsin is rapidly phosphorylated by rhodopsin kinase, which permits the protein arrestin to bind to rhodopsin; bound arrestin blocks the ability of activated rhodopsin to activate transducin, thus effectively truncating the phototransduction cascade
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Acuity is greatest at the center of the macula, a small depression or pit in the retina called the fovea
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Adjustments in the size of the pupil also contribute to the clarity of images formed on the retina; like the images formed by other optical instruments, those generated by the eye are affected by spherical and chromatic aberrations, which tend to blur the retinal image
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After being transported back into the outer segment via IRBP, 11-cis retinal recombines with opsin in the receptor disks
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After silencing ON-center ganglion cells, the animals showed a deficit in their ability to detect stimuli that were brighter than the background; however, they could still see objects that were darker than the background
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All of these events take place within the disk membrane
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Although cones begin to contribute to visual perception at about the level of starlight, spatial discrimination at this light level is still very poor
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Although each transducin molecule activates only one PDE molecule, each PDE is capable of catalyzing the breakdown of as many as 6 cGMP molecules; as a result, the absorption of a single photon by a rhodopsin molecule results in the closure of approximately 200 ion channels, or about 2% of the number of channels in each rod that are open in the dark; this number of channel closures causes a net change in the membrane potential of about 1 mV
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Although it has the same types of functional elements and neurotransmitters found in other parts of the CNS, the retina comprises fewer broad classes of neurons, and these are arranged in a manner that has been less difficult to unravel than circuits in other areas of the brain
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Although the M and L types are the predominant retinal cones, the ratio of M to L varies considerably from individual to individual, as has been shown using optical techniques that permit visualization of identified cone types in the intact human retina
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Although the details of their actions are not entirely clear, horizontal cells are thought to exert their influence via action on photoreceptor terminals, regulating the amount of transmitter that the photoreceptors release onto bipolar cell dendrites
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Although the direction of the potential change may seem odd, the only logical requirement for subsequent visual processing is a consistent relationship between luminance changes and the rate of transmitter release from the photoreceptor terminals
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Although there are differences in the color discrimination capabilities of protanopes and deuteranopes, both have difficulties with the discrimination of red and green, and for this reason dichromacy is commonly called red-green color blindness
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An adjustable pupil thus provides an effective means of reducing oprical aberrations, while maximizing depth of field to the extent that different levels of illumination permit
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Anomalous trichromats may not be aware that they have a color vision deficiency and often pass as normal observers in everyday activities. Dichromats, however, can be severely color deficient, creating safety concerns in some contexts that can limit career opportunities
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Another anatomical feature of the fovea that contributes to the superior acuity of the cone system is the displacement of the inner layers of the retina such that photons are subjected to a minimum of scattering before they strike the photoreceptors
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Another difference is that the response of an individual cone does not saturate at high levels of steady illumination as the rod response does; although both rods and cones adapt to operate over a range of luminance values, the adaptation mechanisms of the cones are more effective
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Another dramatic difference between rod and cone circuitry is their degree of convergence
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Another prominent feature of the fundus is the macula lutea, a circular region containing yellow pigment (xanthophyll) roughly 3 mm in diameter that is located near the center of the retina
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As a result, positive charge (carried by K+) flows out of the cell more rapidly than positive charge (carried by Na+ and Ca2+) flows in, and the cell becomes hyperpolarized
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As a result, the density of rods is much greater than that of cones throughout most of the retina; however, this relationship changes dramatically in the fovea, the highly specialized region in the center of the macula that measures about 1.2 mm in diameter
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As cone density declines with eccentricity and the degree of convergence onto retinal ganglion cells increases, acuity is markedly reduced
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As illumination increases, cones become more and more dominant in determining what is seen, and they are the major determinant of perception under conditions such as normal indoor lighting or sunlight
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As in other nerve cells, transmitter release from the synaptic terminals of the photoreceptor is dependent on voltage-sensitive Ca2+ channels in the terminal membrane
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As noted, the polarity of luminance change (light versus dark) is encoded by different populations of ganglion cells, but these ganglion cells must be sensitive to these changes over the extremely broad range of luminance values that occurs during the typical day and night cycle (almost 109)
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At present there is no cure for color deficiencies. However, experiments in animals that are natural dichromats (in mammals, trichromatic vision is limited to Old World primates) have shown that it is possible to use molecular genetic techniques to express an additional pigment in a subset of cone photoreceptors, and that this manipulation is sufficient to support trichromatic color discriminations. These observations offer the hope that the most serious color deficiencies may eventually be ameliorated by gene therapy
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Because of their antagonistic surrounds, most ganglion cells respond much more vigorously to small spots of light confined to their receptive field centers than to either large spots or to uniform illumination of the visual field. Thus, the information supplied by the retina to central visual stations for further processing does not give equal weight to all regions of the visual scene; rather, it emphasizes the regions where there are spatial differences in luminance: that is, object boundaries
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Because of these facts it should be clear that most of what we think of as normal "seeing" is mediated by the cone system and thus loss of cone function is devastating, as occurs in individuals suffering from macular degeneration
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But about 8% of the male population in the US (and much smaller percentage of the female population) have a deficiency in color vision (color blindness) that manifests as difficulty in distinguishing colors that are easily perceived by individuals with normal trichromatic vision
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By scaling the ganglion cell's response to prevailing levels of illumination (adjusting the gain), the entire dynamic range of a ganglion cell's firing rate can be used to encode information about intensity differences over the range of luminance values that are relevant for a given part of the visual scene. Thus, ganglion cell firing rate is not an absolute measure of light intensity, but a value that reflects the prevailing luminance conditions
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Color vision deficiencies result either from the inherited failure to make one or more of the cone pigments, or from an alteration in the absorption spectra of cone pigments (or rarely, from lesions in the central stations that process color information)
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Combined with evidence from statistical analysis of natural visual scenes showing that dark edges are more numerous, the presence of separate ON-center and OFF-center pathways may be another example of the remarkable power of natural selection to optimize the coding of information in sensory pathways to match the properties of the physical environment
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Compared with ON-center ganglion cells, OFF-center ganglion cells are more numerous and have smaller dendritic fields, endowing them with a capacity for greater spatial resolution
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Consistent with its status as a full-fledged part of the central nervous system, the retina exhibits complex neural circuitry that converts the graded electrical activity of specialized photosensitive neurons—the photoreceptors—into action potentials that travel to central targets via axons in the optic nerve
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Convergence makes the rod system a better detector of light, because small signals from many rods are pooled to generate a large response in the bipolar cell; at the same time, convergence reduces the spatial resolution of the rod system, since the source of a signal in a rod bipolar cell or retinal ganglion cell could have come from anywhere within a relatively large area of the retinal surface; the one-to-one relationship of cones to bipolar and ganglion cells is what is required to maximize acuity
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Conversely, the cone system has very high spatial resolution but is relatively insensitive to light; it is specialized for acuity at the expense of sensitivity; the properties of the cone system also allow humans and many other animals to see color
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Conversely, the exclusion of rods from the fovea, and their presence in high density away from the fovea, explains why the threshold for detecting a light stimulus is lower outside the region of central vision... It is easier to see a dim object by looking slightly away from it, so that the stimulus falls on the region of the retina that is richest in rods
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Decrements in light intensity naturally have the opposite effect on these two classes of bipolar cells, hyperpolarizing ON-center cells and depolarizing OFF-center ones
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Despite its peripheral location, the retina, which is the neural portion of the eye, is actually part of the central nervous system
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Despite the aesthetic pleasure inherent in having color vision, most of the information in visual scenes consists of spatial variations in light intensity; a black and white movie, for example, has most of the information a color version has, although it is deficient in some respects and may be less interesting to watch
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Despite the fact that perception in typical daytime light levels is dominated by cone-mediated vision, the total number of rods in the human retina (about 90 million) far exceeds the number of cones (roughly 4.5 million)
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Differences in the transduction mechanisms utilized by the two receptor types are a major factor in the ability of rods and cones to respond to different ranges of light intensity
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During development, the retina forms as an out-pocketing of the diencephalon called the optic vesicle
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Dynamic changes in the shape of the lens are referred to as accommodation
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Each rod bipolar cell is contacted by a number of rods, and many rod bipolar cells contact a given amacrine cell; in contrast, the cone system is much less convergent
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Figure 11.19 shows how the response rate of an ON-center ganglion cell to a small spot of light turned on in its receptive field center varies as a function of the spot's intensity. The response rate is roughly proportional to the spot's intensity over a range of about 1 log unit
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Finally, the decrease of Ca2+ increases the affinity of the cGMP-gated channels for cGMP, reducing the impact of the light-induced reduction of cGMP levels
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Focusing on closer objects requires relaxing the tension in the zonule fibers, allowing the inherent elasticity of the lens to increase its curvature
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For example, some dichromats lack the green pigment gene altogether, while others have a hybrid gene that is thought to produce a redlike pigment in the "green" cones. Anomalous trichromats also possess hybrid genes, but these genes elaborate pigments whose spectral properties lie between those of the normal red and green pigments
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For some of these individuals, color vision is dichromatic: only two bandwidths of light are needed to match all the colors that can be perceived; the two most prevalent forms of dichromacy are protanopia, characterized by impairment in perception of long wavelengths, and deuteranopia, impairment in the perception of medium wavelengths
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Glutamate release from photoreceptor terminals has a depolarizing effect on horizontal cells (sign-conserving synapse), while horizontal cells have a hyperpolarizing influence on photoreceptor terminals (sign-inverting synapse); as a result, the net effect of inputs from the horizontal cell network is to oppose changes in the membrane potential of the photoreceptor that are induced by phototransduction events in the outer segment
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Graded depolarization of bipolar cells leads to an increase in transmitter release (glutamate) at their synapses and consequent depolarization of the ON-center ganglion cells that they contact via AMPA, kainate, and NMDA receptors
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Horizontal cells receive synaptic inputs from photoreceptor terminals and are linked via gap junctions with a vast network of other horizontal cells distributed over a wide area of the retinal surface. As a result, the activity in horizontal cells reflects levels of illumination over a broad area of the retina
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However, the intensity of spot illumination required to evoke a given discharge rate is dependent on the level of illumination in the receptive field center prior to the onset of the spot. Increases in background level of illumination are accompanied by adaptive shifts in the ganglion cell's operating range such that greater stimulus intensities are required to achieve the same discharge rate
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In addition to being a conspicuous retinal landmark, the appearance of the optic disk provides a useful gauge of intracranial pressure
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In addition to efficiently transmitting light energy, the primary function of the optical components of the eye is to generate a focused image on the surface of the retina
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In contrast, ON-center bipolar cells express a G-protein-coupled metabotropic glutamate receptor (mGluR6). When bound to glutamate, these receptors activate an intracellular cascade that closes cGMP-gated Na+ channels, reducing inward current and hyperpolarizing the cell
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In most parts of the retina, rod and cone signals converge on the same ganglion cells; that is, individual ganglion cells respond to both rod and cone inputs, depending on the level of illumination
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In order to understand the response of ON- and OFF-center bipolar cells to changes in light intensity, recall that photoreceptors hyperpolarize in response to light increments, decreasing their release of neurotransmitter; under these conditions, ON-center bipolar cells contacted by the photoreceptors are freed from the hyperpolarizing influence of the photoreceptor's transmitter, and they depolarize. ln contrast, for OFF-center cells, the reduction in glutamate represents the withdrawal of a depolarizing influence, and these cells hyperpolarize
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In the dark, cations (both Na+ and Ca2+) flow into the outer segment through membrane channels that are gated by the nucleotide cyclic guanosine monophosphate (cGMP) similar to other second-messenger systems
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In the dark, the receptor is in a depolarized state, with a membrane potential of roughly -40 mV (including those portions of the cell that release transmitters)
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In the fovea (which literally means "pit"), cone density increases almost 200-fold, reaching, at its center, the highest receptor packing density anywhere in the retina
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In the light, when receptors are hyperpolarized, the number of open Ca2+ channels is reduced, and the rate of transmitter release is also reduced; the reason for this unusual arrangement compared with that in other sensory receptor cells is not known, but it may have to do with the challenge of responding to both increases and decreases of luminance
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In the retina, photoreceptors do not exhibit action potentials; rather, light activation causes a graded change in membrane potential and a corresponding change in the rate of transmitter release onto postsynaptic neurons
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Indeed, much of the processing within the retina is mediated by graded potentials, largely because action potentials are not required to transmit information over the relatively short distances involved
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Indeed, opacities in the lens known as cataracts account for roughly half the cases of blindness in the world, and almost everyone over the age of 70 experiences some loss of transparency in the lens that ultimately degrades the quality of vision; fortunately, successful surgical treatments for cataracts can restore vision in most cases
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Interestingly, large differences in the ratio of M to L cone types (from nearly 4:1 to 1:1) do not appear to have much impact on color perception
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It is impossible, therefore, to determine whether the change in the membrane potential of a particular cone has arisen from exposure to many photons at wavelengths to which the receptor is relatively insensitive, or fewer photons at wavelengths to which it is most sensitive
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It is logical to suppose that a visual field defect, or scotoma, would be seen; however, they often go unnoticed; in fact, all of us have a physiological scotoma, i.e., the blind spot
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Just 6 degrees eccentric to the line of sight, acuity is reduced by 75%, a fact that can be readily appreciated by trying to read the words on any line of this page beyond the word fixated on
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Kuffler's work also called attention to the fact that retinal ganglion cells do not act as simple photodetectors. Indeed, most ganglion cells are relatively poor at signaling differences in the level of diffuse illumination. Instead, they are sensitive to differences between the level of illumination that falls on the receptive field center and the level of illumination that falls on the surround—that is, to luminance contrast
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Like the mechanism responsible for generating the ON- and OFF-center response, the antagonistic surround of ganglion cells is thought to be a product of interactions that occur at the early stages of retinal processing. Much of the antagonism is believed to arise via lateral connections established by horizontal cells and receptor terminals
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Mesopic vision occurs in levels of light at which both rods and cones contribute—at twilight, for instance
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Most of what is known about the molecular events of phototransduction has been gleaned from experiments in rods, in which the photopigment is rhodopsin
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Normal trichromats have one gene for the red pigments and can have anywhere from one to five genes for green pigments. In contrast, the blue-sensitive pigment gene, found on chromosome 7, is quite different in its amino acid sequence
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Normal vision requires that the optical media of the eye be transparent, and both the cornea and the lens are remarkable example, achieving a level of transparency that rival that found in inorganic materials such as glass
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Not surprisingly, alterations in the composition of the cornea or the lens can significantly reduce their transparency and have serious consequences for visual perception
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Numerous blood vessels, both arteries and veins, fan out over the inner surface of the retina; these blood vessels arise from the ophthalmic artery and vein, which enter or leave the eye through a whitish circular area known as the optic disc, or optic papilla
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OFF-center bipolar cells have ionotropic receptors (AMPA and kainate) that cause the cells to depolarize in response to glutamate released from photoreceptor terminals
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OFF-center ganglion cells exhibit a similar surround antagonism with reversed polarity: the increase in response that occurs to the presentation of a dark spot that fills the center of an OFF-center ganglion cell receptive field is reduced when the dark spot extends into the receptive field surround
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ON- and OFF-center ganglion cells have dendrites that arborize in separate strata of the inner plexiform layer, forming synapses selectively with the terminals of ON and OFF-center bipolar cells that respond to luminance increases and decreases, respectively
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Once initiated, additional mechanisms limit the duration of this amplifying cascade and restore the various molecules to their inactive states
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One of the important features of this complex biochemical cascade initiated by photon capture is that it provides enormous signal amplification; a single light-activated rhodopsin molecule can activate as many as 800 transducin molecules—roughly 8% of the transducin molecules on the disk surface
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People who have lost cone function are legally blind, whereas those who have lost rod function only experience difficulty seeing at low levels of illumination (night blindness)
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Perceiving color allows humans and many other animals to discriminate objects on the basis of the distribution of the wavelengths of light that they reflect to the eye; while differences in luminance are often sufficient to distinguish objects, color adds another perceptual dimension that is especially useful when differences in light intensity are subtle or nonexistent
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Perhaps even more surprising is that shining light on a photoreceptor, either a rod or a cone, leads to membrane hyperpolarization rather than depolarization
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Peter Schiller and his colleagues at MIT, who examined the effects of pharmacologically inactivating ON-center ganglion cells on a monkey's ability to detect visual stimuli, suggested a rationale for having two distinct types of retinal ganglion cells
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Photoreceptor synapses with OFF-center bipolar cells are described as sign-conserving, since the sign of the change in membrane potential of the bipolar cell (depolarization or hyperpolarization) is the same as that in the photoreceptor
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Photoreceptor synapses with ON-center bipolar cells are called sign-inverting because the change in the membrane potential of the bipolar cell is the opposite of that in the photoreceptor
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Photoreceptors are most sensitive to light at lower levels of illumination; as levels of illumination increase, sensitivity decreases, preventing the receptors from saturating and thereby greatly extending the range of light intensities over which they operate
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Progressive increases in the intensity of illumination cause the potential across the receptor membrane to become more negative, a response that saturates when the membrane potential reaches roughly -65 mV
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Reducing the size of the pupil also increases the depth of field—that is, the distance within which objects are seen without blurring; however, a small pupil also limits the amount of light that reaches the retina, and under conditions of dim illumination, visual acuity becomes limited by the number of available photons rather than by optical aberrations
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Rods produce a reliable response to a single photon of light, whereas more than 100 photons are required to produce a comparable response in a cone; it is not true, however, that cones fail to effectively capture photons—rather, the change in current produced by a single photon capture in cones is comparatively small and difficult to distinguish from the background noise
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S cones make up only about 5-10% of the cones in the retina, and they are virtually absent from the center of the fovea
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Several lines of evidence indicate that adjustments in the gain of ganglion cell response are due to changes that occur beyond the level of the photoreceptor. In particular, dynamic regulation of neurotransmitter release within the bipolar cell terminal is thought to play a major role in ganglion cell adaptation. Other factors such as synaptic inputs from amacrine cells and mechanisms intrinsic to ganglion cells' spike generation mechanism are also implicated
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Since these aberrations are greatest for light rays that pass farthest from the center of the lens, narrowing the pupil reduces both spherical and chromatic aberration, just as closing the iris diaphragm on a camera lens improves the sharpness of a photographic image
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Some anomalous trichromats require higher intensity long-wavelength stimulation to make color matches (protanomalous trichromats), while others require higher intensity medium-wavelength (deuteranomalous trichromats) or short-wavelength (tritanomalous trichromats) stimulation
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Stephen Kuffler, working at Johns Hopkins University, pioneered this approach in mammals early in the 1950s, when he characterized the responses of single ganglion cells in the cat retina. He found that each ganglion cell responds to stimulation of a small circular patch of the retina, which defines the cell's receptive field; based on these responses, Kuffler distinguished two classes of ganglion cells, ON-center and OFF-center
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The all-trans retinal dissociates from opsin and diffuses into the cytosol of the outer segment; there it is converted to all-trans retinol and transported into the pigment epithelium via a chaperone protein, interphotoreceptor retinoid binding protein (IRBP), where appropriate enzymes ultimately convert it to 11-cis retinal
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The arrangement of the circuits that transmit rod and cone information to retinal ganglion cells also contributes to the different characteristics of scotopic and photopic vision
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The cell bodies and processes of these neurons are stacked in alternating layers, with the cell bodies located in the inner nuclear, outer nuclear, and ganglion cell layers, and the processes and synaptic contacts located in the inner plexiform and outer plexiform layers
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The cells that make up the retinal pigment epithelium have long processes that extend into the photoreceptor layer, surrounding the tips of the outer segments of each photoreceptor
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The center of a ganglion cell receptive field is surrounded by a concentric region that, when stimulated, antagonizes the response to stimulation of the receptive field center; for example, presentation of a small spot of light in the center of the receptive field of an ON-center ganglion cell generates a response that is enhanced as the spot size increases, but once the size of the spot exceeds the receptive field center and enters the surround, further increases in the diameter of the stimulus lead to a progressive decrease in the cell's response
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The changes in opsin lead, in turn, to the activation of an intracellular messenger called transducing, which activates a phosphodiesterase (PDE) that hydrolyzes cGMP
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The concentration of Ca2+ in the outer segment appears to play a key role in the light-induced modulation of photoreceptor sensitivity; the cGMP-gated channels in the outer segment are permeable to both Na+ and Ca2+ and thus light-induced closure of these channels leads to a net decrease in the internal Ca2+ concentration
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The contributions of rods to vision drops out nearly entirely in photopic vision because their response to light saturates—that is, the membrane potential of individual rods no longer varies as a function of illumination because all of the membrane channels are closed
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The cornea and lens are primarily responsible for the refraction of light necessary for focused images on the retina
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The cornea contributes most of the necessary refraction, as can be appreciated by considering the hazy, out-of-focus images experienced when swimming underwater. Water, unlike air, has a refractive index close to that of the cornea; as a result, immersion in water virtually eliminates the refraction that normally occurs at the air-cornea interface; thus, the image is no longer focused on the retina
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The decrease in Ca2+ also increases the activity of rhodopsin kinase, permitting more arrestin to bind to rhodopsin
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The different opsins tune the molecule's absorption of light to a particular region of the light spectrum; indeed, it is the differing protein components of the photopigments in rods and cones that allow the functional specialization of these two receptor types
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The difficulty of making fine visual discriminations under very low light conditions where only the rod system is active is a common experience; the problem is primarily the poor resolution of the rod system (and to a lesser extent, the fact that there is no perception of color because in dim light there is no significant involvement of the cones)
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The early stages of the pathways that link rods and cones to ganglion cells, however, are largely independent—for example, the pathway from rods to ganglion cells involves a distinct class of rod bipolar cells that, unlike cone bipolar cells, do not contact retinal ganglion cells; instead, the rod bipolar cells synapse with the dendritic processes of a specific class of amacrine cells that makes gap junctions and chemical synapses with the terminals of cone bipolars; these processes then make synaptic contacts on the dendrites of ganglion cells in the inner plexiform layer
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The extremely high density of cone receptors in the fovea, coupled with the one-to-one relationship with bipolar cells and retinal ganglion cells, endows this component of the cone system with the capacity to mediate the highest levels of visual acuity
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The figure shows the range of illumination over which the rods and cones operate; at the lowest levels of illumination only the rods are activated—such rod-mediated perception is called scotopic vision
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The fovea is also devoid of another source of optical distortion that lies in the light path to the receptors elsewhere in the retina—the retinal blood vessels; this avascular central region of the fovea is thus dependent on the underlying choroid and pigment epithelium for oxygenation and metabolic sustenance
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The genes that encode the red and green pigments show a high degree of sequence homology and lie adjacent to each other on the X chromosome, thus explaining the prevalence of red-green color deficiency in males
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The hydrolysis by PDE at the disk membrane lowers cGMP concentration throughout the outer segment, thus reducing the number of cGMP molecules available to bind to the channels in the surface of the outer segment membrane and leading in turn to channel closure
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The increased density of cones in the fovea is accompanied by a sharp decline in the density of rods; the central 300 um of the fovea, called the foveola, is totally free of rods
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The lens has considerably less refractive power than the cornea; however, the refraction supplied by the lens is adjustable, allowing the observer to bring objects at various distances into sharp focus
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The macula is the region of the retina that supports high visual acuity (the ability to resolve fine details)
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The magnitude of the phototransduction amplification varies with the prevailing level of illumination, a phenomenon known as light adaptation
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The majority of individuals with color vision deficiencies, however, are anomalous trichromats; in this condition, three light sources (short medium, and long wavelengths) are needed to make all possible color matches; but the matches are made using intensity values significantly different from those used by most individuals
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The mechanisms by which central targets decipher the spatial patterns of light and dark that fall on the photoreceptors have been a vexing problem
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The much larger axons of the ganglion cells form the optic nerve and carry information about retinal stimulation to the rest of the CNS
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The optic disk is also where retinal axons leave the eye to reach targets in the thalamus and midbrain via the optic nerve
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The other form of dichromacy, tritanopia, is extremely rare; tritanopes have impaired perception of short wavelengths, a condition commonly called blue-yellow color blindness
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The photopigment contains the light-absorbing chromophore retinal (an aldehyde of vitamin A) coupled to one of several possible proteins called opsins
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The photoreceptors comprise two types, rods and cones; both types have an outer segment adjacent to the pigment epithelium that contains membranous disks with light-sensitive photopigment, and an inner segment that contains the cell nucleus and gives rise to synaptic terminals that contact bipolar or horizontal cells
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The pigment epithelium plays two roles that are critical to the function of retinal photoreceptors—first, the membranous disks in the outer segment, which house the light-sensitive photopigment and other proteins involved in phototransduction, have a lifespan of only about 12 days; new outer segment disks are continuously being formed near the base of the outer segment, while the oldest disks move progressively from the base of the outer segment to the tip, where the pigment epithelium plays an essential role in removing the expended receptor disks; this shedding involves the "pinching off" of a clump of receptor disks by the outer segment membrane of the photoreceptor—second is to regenerate photopigment molecules after they have been exposed to light; photopigment is cycled continuously between the outer segment of the photoreceptor and the pigment epithelium
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The pigment xanthophyll has a protective role, filtering ultraviolet wavelengths that could be harmful to the photoreceptors; damage to this region of the retina, as occurs in age-related macular degeneration, has a devastating impact on visual perception
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The principal difference between ganglion cells and bipolar cells lies in the nature of their electrophysiological responses; like most other cells in the retina, bipolar cells have graded potentials rather than action potentials
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The processes of amacrine cells are postsynaptic to bipolar cell terminals and presynaptic to the dendrites of ganglion cells; different subclasses of amacrine cells are thought to make distinct contributions to visual function; for example, one amacrine cell type has an obligatory role in the pathway that transmits information from rod photoreceptors to retinal ganglion cells—another is critical for generating the direction-selective responses exhibited by a specialized subset of ganglion cells
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The processes of horizontal cells enable lateral interactions between photoreceptors and bipolar cells that maintain the visual system's sensitivity to contrast, over a wide range of light intensities, or luminance
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The reason for this curious feature of retinal organization is the special relationship that exists among the outer segments of the photoreceptors and the pigment epithelium
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The receptive fields of ON- and OFF-center ganglion cells have overlapping distributions in visual space, so several ON-center and several OFF-center ganglion cells analyze every point on the retinal surface (i.e., every part of visual space)
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The reduction in activity of the horizontal cells has a depolarizing effect on the membrane potential of the central photoreceptor, reducing the lightevoked response, and ultimately reducing the firing rate of the ON-center ganglion cell
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The regulatory effects of Ca2+ on the phototransduction cascade are only one part of the mechanism that adapts retinal sensitivity to background levels of illumination; another important contribution comes from neural interactions between horizontal cells and photoreceptor terminals
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The restoration of retinal to a form capable of signaling photon capture is a complex process known as the retinoid cycle
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The restriction of highest acuity vision to such a small region of the retina is the main reason humans spend so much time moving their eyes (and heads) around—in effect directing the foveae of the two eyes to objects of interest; it is also the reason why disorders that affect the functioning of the fovea have such devastating effects on sight
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The retinoid cycle is critically important for maintaining the light sensitivity of photoreceptors; even under intense illumination, the rate of retinal regeneration is sufficient to maintain a significant number of active photopigment molecules
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The rod system has very low spatial resolution but is extremely sensitive to light; it is therefore specialized for sensitivity at the expense of seeing detail
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The selective response of ON- and OFF-center bipolar cells to light increments and decrements is explained by the fact that they express different types of glutamate receptors
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The series of biochemical changes that ultimately leads to a reduction in cGMP levels begins when a photon is absorbed by the photopigment in the receptor disks
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The seven transmembrane domains of the opsin molecule traverse the membrane of the disks in the outer segment, forming a pocket in which the retinal molecule resides
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The shape of the lens is determined by two opposing forces—the elasticity of the lens, which tends to keep it rounded up (removed from the eye, the lens becomes spheroidal); and the tension exerted by the zonule fibers, which tends to flatten it
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The short azonal processes of bipolar cells make synaptic contacts on the dendritic processes of ganglion cells in the inner plexiform layer
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The size of the pupil is controlled by innervation from both sympathetic and parasympathetic divisions of the visceral motor system, which in turn are modulated by several brainstem centers
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The spatial arrangement of retinal layers at first seems counterintuitive—light rays must pass through various non-light-sensitive elements of the retina as well as the retinal vasculature before reaching the outer segments of the photoreceptors where photons are absorbed
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The subarachnoid space surrounding the optic nerve is continuous with that of the brain; as a result, increases in intracranial pressure—a sign of serious neurological problems such as space-occupying lesions or brain swelling due to trauma—can be detected as a protuberance of the optic disk
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The synapses between the photoreceptor terminals and bipolar cells (and horizontal cells) occur in the outer plexiform layer, the cell bodies of photoreceptors making up the outer nuclear layer, and the cell bodies of bipolar cells making up the inner nuclear layer
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The trichromatic nature of color vision is supported by perceptual studies showing that any color stimulus can be matched to a second stimulus composed of three superimposed light sources (long, medium, and short wavelengths), provided the intensity of the light sources can be independently adjusted
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The two other types of neurons in the retina, horizontal and amacrine cells, have their cell bodies in the inner nuclear layer and have processes that are limited to the outer and inner plexiform layer, respectively
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The two types of photoreceptors, rods and cones, are distinguished by their shape (from which they derive their names), the type of photopigment they contain, their distribution across the retina, and their pattern of synaptic connections
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There are five basic classes of neurons in the retina: photoreceptors, bipolar cells, ganglion cells, horizontal cells, and amacrine cells
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These changes arise from the tension of the ciliary muscle that surrounds the lens; the lens is held in place by radially arranged connective tissue bands called zonule fibers that are attached to the ciliary muscle
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These considerations, along with the fact that the capillaries in the choroid underlying the pigment epithelium are the primary source of nourishment for retinal photoreceptors, presumably explain why rods and cones are found in the outermost rather than the innermost layer of the retina; indeed, disruption in this normal relationship between the pigment epithelium and retinal photoreceptors have severe consequences for vision
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These facts suggest that the red and green pigment genes evolved relatively recently, perhaps as a result of the duplication of a single ancestral gene; they also explain why most color vision abnormalities involve the red and green cone pigments
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These observations imply that information about increases or decreases in luminance is carried separately to the brain by reciprocal changes in the activity of these two types of retinal ganglion cells
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These properties reflect the fact that the rod and cone systems (the receptor cells and their connections within the retina) are specialized for different aspects of vision
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This ambiguity can be resolved only by comparing the activity in different classes of cones; based on the responses of individual ganglion cells and cells at higher levels in the visual pathway, comparisons of this type are clearly involved in how the visual system extracts color information from spectral stimuli, although a full understanding of the neural mechanisms that underlie color perception has been elusive
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This decrease triggers a number of changes in the phototransduction cascade, all of which tend to reduce the sensitivity of the receptor to light; for example, the decrease in Ca2+ increases the activity of guanylate cyclase, the cGMP-synthesizing enzyme, leading to increased cGMP levels
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This difference in adaptation is apparent in the time course of the response of rods and cones to light flashes; the response of a cone, even to a bright light flash that produces the maximum change in photoreceptor current, recovers in about 200 ms—more than 4x faster than rod recovery
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This high density is achieved by decreasing the diameter of the cone outer segments such that foveal cones resemble rods in their appearance;
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This inward current is opposed by an outward current that is mediated by potassium-selective channels in the inner segment; thus, the depolarized state of the photoreceptor in the dark reflects the net contribution of Na+ and Ca2+ influx, which acts to depolarize the cell, and K+ efflux, which acts to hyperpolarize the cell
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This nomenclature can be a bit misleading in that it seems to imply that individual cones provide color information for the wavelength of light that excites them best; in fact, individual cones, like rods, are entirely color-blind in that their response is simply a reflection of the number of photons they capture, regardless of the wavelength of the photon (or more properly, vibrational energy)
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This region of the retina contains no photoreceptors and, because it is insensitive to light, produces the perceptual phenomenon known as the "blind spot"
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This relaxation is accomplished by the sphincter-like contraction of the ciliary muscle; because the ciliary muscle forms a ring around the lens, when the muscle contracts, the attachment points of the zonule fibers move toward the central axis of the eye, thus reducing the tension on the lens
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Thus, ON-center cells increase their discharge rate to luminance increments in the receptive field center; whereas OFF-center cells increase their discharge rate to luminance decrements in the receptive field center
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Thus, although most anomalous trichromats have distinct sets of medium- and long-wavelength cones, there is more overlap in their absorption spectra than in normal trichromats, and thus less difference in how the two sets of cones respond to a given wavelength, with resulting anomalies in color perception
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Thus, each of the retinal ganglion cells that dominate central vision (midget ganglion cells) receives input from only one cone bipolar cell, which, in turn, is contacted by a single cone
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Thus, even at the earliest stages in visual processing, neural signals do not represent the absolute numbers of photons that are captured by a receptor, but rather the relative intensity of stimulation—how much the current level of stimulation differs from previous stimulation levels, and how much it differs from the activity of neurons in adjacent areas of the retina
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Thus, glutamate has opposite effects on these two classes of cells, depolarizing OFF-center bipolar cells and hyperpolarizing ON-center cells
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Thus, in the dark, when photoreceptors are relatively depolarized, the number of open Ca2+ channels in the synaptic terminal is high, and the rate of transmitter release is correspondingly great
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Thus, normal human color vision is fundamentally trichromatic, based on the relative levels of activity in three sets of cones that have different absorption spectra
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To find the blind spot of right eye cover the left eye and fixate on a small mark made on left side of a sheet of paper; then, without breaking fixation on the mark, move the tip of a pencil slowly toward it from the right side of the page; at some point about the middle of the sheet, the tip of the pencil will disappear
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To understand what the complex neural circuits within the retina accomplish during this process, it is useful to begin by considering the responses of individual retinal ganglion cells to small spots of light
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Turning on a spot of light in the receptive field center of an ON-center neuron produces a burst of action potentials; the same stimulus applied to the receptive field center of an OFF-center neuron reduces the rate of discharge, and when the spot of light is turned off, the cell responds with a burst of action potentials; complementary patterns of activity are found for each cell type when a dark spot is placed in the receptive field center
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Under these conditions, changes in the membrane potential of the horizontal cells that synapse with the photoreceptor terminal are relatively small, and the response of the photoreceptor to light is largely determined by its phototransduction cascade
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Unlike rods, which contain a single photopigment, the three types of cones are defined by the photopigment they contain; each photopigment is differentially sensitive to light of different wavelengths, and for this reason cones are referred to as blue, green, and red—or more appropriately, short- (S-), medium- (M-), and long- (L-) wavelength cones; which more or less describes their spectral sensitivities
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We have already considered the specializations in the rod and cone systems and the adaptation mechanisms in the phototransduction cascade that adjust the sensitivity of the retina to these dramatically different light intensities. But even within a single visual scene there are significant differences in light intensity that must be accommodated quickly by the visual system as we make rapid and frequent eye movements to objects of interest
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When retinal absorbs a photon of light, one of the double bonds between the carbon atoms in the retinal molecule breaks, and its configuration changes from the 11-cis isomer to all-trans retinal; this change triggers a series of alteration in the opsin component of the molecule
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When viewing distant objects, the force exerted by the zonule fibers is greater than the elasticity of the lens, and the lens assumes the flatter shape appropriate for distance viewing
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When viewing distant objects, the lens is made relatively thin and flat and has the least refractive power. For near vision, the lens becomes thicker and rounder and has the most refractive power
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Why there are separate "channels" for light and dark remains unclear, although there is increasing evidence that there are additional differences in the morphology and the response properties of ON- and OFF-center ganglion cells that are important to consider
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With both eyes open, information about the corresponding region of visual space is available from the temporal retina of the other eye; but this does not explain why the blind spot remains undetected with one eye closed; when the world is viewed monocularly, the visual system simply "fills in" the missing part of the scene; to observe filling in, notice what happens when the pencil lies across the optic disk representation, about 5-8 degrees in diameter—remarkably, it looks complete
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With the addition of light to the surround, however, the impact of the horizontal network becomes significantly greater; the light-induced reduction in the release of glutamate from the photoreceptors in the surround leads to a strong hyperpolarization of the horizontal cells whose processes converge on the terminal of the photoreceptor in the receptive field center
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Human dichromats lack one of the three cone pigments, either because the corresponding gene is missing or because it exists as a hybrid of the red and green pigment genes
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Using an ophthalmoscope, the surface of the retina, called the fundus, can be visualized through the pupil