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Home , Amacrine cell, Inner plexiform layer, Night vision, Outer plexiform layer, Retina

How the Works

Much of the construction of an image takes place in the retina itself through the use of specialized neural circuits

Helga Kolb

he retina is a filmy piece of tissue, fixed in the photoreceptors’ pro- Most other mammalian also Tbarely half a millimeter thick, that teins, where this small molecule have a preponderance of rods, and the lines the inside of the eyeball. The tis- changes its conformation in response cones are often concentrated in special- sue develops from a pouch of the em- to , or packets of . Once ized regions. In species such as bryonic , and the retina is molecules are exposed to light and , images focus to a central therefore considered part of the . and undergo their conformational specialized area, aptly called the area This most important part of the change, they are recycled back into the centralis, where cones predominate. has a basic structure similar to that of a pigment epithelium. This tissue be- The retinas of mammals such as rab- three-layer cake, with the bodies of hind the retina is usually very dark bits and squirrels, as well as those of cells arrayed in three rows sepa- because its cells are full of melanin nonmammals like , have a long, rated by two layers packed with granules. The pigment granules ab- horizontal strip of specialized cells synaptic connections. The retina in- sorb stray photons, preventing their called a visual streak, which can detect cludes both the sensory that reflection back into the photorecep- the fast movement of predators. Pri- respond to light and intricate neural tors, which would cause images to mates as well as some have front- circuits that perform the first stages of blur. They also protect the cells from projecting allowing binocular vi- image processing; ultimately, an elec- too much exposure to light radiation. sion and thus depth ; their trical message travels down the optic eyes are specialized for good daylight nerve into the brain for further pro- Retina Design According to Lifestyle vision and are able to discriminate col- cessing and . All retinas contain at least or and fine details. and rap- Intuitively, one might expect that two types of photoreceptors—the fa- tors, like eagles and , have a the surface of the retina (the layer ex- miliar rods and cones. Rods are gener- fovea, a tremendously cone-rich spot posed to the liquid in the eyeball’s vit- ally used for low-light vision and cones devoid of rods where images focus. reous chamber) would contain the for daylight, bright-colored vision. The Primates, in fact, have what is called sensory cells, the photoreceptors, but variations among animal eyes reveal a duplex retina, allowing good visual actually these cells lie at the very back adaptations to the different environ- discrimination in all condi- of the retina; light rays must pass ments in which they live. Most , tions. The fovea contains most of the through the entire retina before reach- frog, and retinas have three cones, packed together as tightly as ing pigment molecules to excite. This to five types of cones and consequently physically possible, and allows good is because the pigment-bearing mem- very good vision. Keep in mind daylight vision. More peripheral parts branes of the photoreceptors have to that and fish are “cold blood- of the retina can detect the slightest be in contact with the eye’s pigment ed” and need to be active in the warm glimmer of photons at night. Most epithelial layer, which provides a daytime. Most mammals have retinas mammals have two types of cones, steady stream of the vital molecule, in which rods predominate. When the green-sensitive and blue-sensitive, but retinal or . Retinal becomes number of mammals started to ex- primates have three types—red-sensi- plode as the dinosaurs died out, the tive as well as the other two. With our Helga Kolb is professor emeritus of Earth was likely a dark place covered cone vision, we can see from gray and visual sciences at the . She in ash and clouds; the tiny, fur-covered dawn to the dazzling conditions of studied at the University of Bristol, completing her early mammals were able to generate high noon with the sun burning down Ph.D. in 1971. She conducted eye research at the their own body heat and developed on white sand. Initially the cone photo- Institute of Ophthalmology in London, where she visual systems sensitive to dim light. receptors themselves can adapt to the became involved in studies of and Modern rodents such as rats and mice, surrounding brightness, and circuitry anatomy, and later moved to positions at Johns Hopkins and the National Institutes of Health. She which are nocturnal animals, still have through the retina can further modu- joined the Utah faculty in 1979. Address: Univer- retinas overwhelmingly dominated by late the eye’s response. Similarly, the sity of Utah Health Sciences Center, 75 North rods; their cones are small in size and rod photoreceptors and the neural cir- Medical Drive, Salt Lake City, Utah 84132. Inter- only make up 3 to 5 percent of their cuitry to which they connect can adapt net: [email protected] photoreceptors. to lower and lower intensity of light. © 2003 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. 28 American Scientist, Volume 91 Figure 1. Intricately wired neurons in the retina allow a good deal of image assembly to take place in the eye itself. The author estimates that sci- entists understand about half of the interactions among the cells in this delicate piece of tissue. In this rendering, light enters the eye from the left. The photons travels through the vitreous fluid of the eyeball and penetrate the entire retina, which is about half a millimeter thick, before reaching the photoreceptors—the cones and rods that respond to light (the colored and black cells attached to the epithelium at right). Signals then pass from the photoreceptors through a series of neural connections toward the surface of the retina, where the ganglion-cell nerve-fiber layer relays the processed information to the and into the brain. (Drawing by the author.)

Anatomy and Physiology Imaging techniques ranging from old- like those observed in other neurons. Understanding the anatomy of the pri- style Golgi silver staining, first used However, the first recordings of im- mate retina is essential to understand- over a century ago by Ramón y Cajal, pulses within the retina by Gunnar ing its function. Again, the photore- to electron microscopy and modern- Svaetichin in the 1950s showed very ceptors lie in a layer against the back day antibody staining have revealed odd responses to light. Neurons in the of the eyeball. In the second of three the shapes and sizes of the retina’s cell outer retina—it was not immediately cell layers, called the inner nuclear lay- types and how the different cells con- clear which cells he was recording er, lie one to four types of horizontal nect to form . Staining tech- from—responded to stimulation not cells, 11 types of bipolar cells and 22 to niques have revealed electrical junc- with depolarizing spikes but with slow 30 types of amacrine cells. The numbers tions between cells and the identity hyperpolarization. These “S potentials” vary depending on species. The sur- and location of recep- are now known to originate with the face layer of the retina contains about tors and transporters. We now know photoreceptors and to be transmitted to 20 types of ganglion cells. Impulses that the neurotransmitter (chemical horizontal cells and bipolar cells. The from the ganglion cells travel to the signal) passed through the vertical membrane hyperpolarization starts on brain via more than a million optic pathways of the retina—from photore- exposure to light, follows the time nerve fibers. The spaces separating ceptors to bipolar cells to ganglion course of a light and then returns these three layers are also anatomically cells—is glutamate. The horizontal and to the baseline value when the light is distinct. The region containing synaps- amacrine cells send signals using vari- off. This reflects the counterintuitive es linking the photoreceptors with ous excitatory and inhibitory amino fact that both rods and cones release bipolar and horizontal cell dendrites is acids, catecholamines, peptides and ni- during the dark, known as the ; the tric oxide. when the membrane is depolarized area where the bipolar and amacrine Electrophysiological investigations and sodium ions flow freely across the cells connect to the ganglion cells is the of the retina started 60 years ago. Stud- photoreceptors’ cell membranes. When . ies of the optic nerve fibers showed that exposed to light, ion channels in the Decades of anatomical studies have they could be stimulated to give tradi- cell membranes close. The cells go into shed light on how the retina works. tional depolarizing action potentials, a hyperpolarized state for as long as © 2003 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. 2003 January–February 29 cells to respond to photoreceptor input pigment epithelium differently (Figure 7). Some bipolar cells are tuned to faster and some to slower retina fluctuations in the visual signal; some photoreceptors glutamate receptors resensitize rapidly outer plexiform and others more gradually. The cells inner nuclear inner plexiform thus fire either quickly in succession or relatively slowly in response to the ganglion cells same amount of stimulation. These re- ceptors respond to glutamate by acti- vating what’s known as an OFF path- way in the visual process, detecting optic dark images against a lighter back- nerve ground. (Recall that photoreceptors ciliary constantly release glutamate unless ex- body posed to light.) Other bipolar cells have inhibitory glutamate receptors; Figure 2. Diagram of a shows its various structures (left). A thin piece of retina is enlarged in a photomicrograph (right), revealing its layers. The photoreceptors lie against a in other words, they prevent the bipo- dark row of cells called the pigment epithelium. (Drawing by the author. Except where noted, lar cell from firing when the cell is ex- photographs by Nicolas Cuenca and the author.) posed to the neurotransmitter. These receptors activate the ON pathway, de- the light continues to shine on them images into separate parts. Both rods tecting light images against a darker and do not release a neurotransmitter. and cones respond to light directly background. Although both rods and cones re- over them. Thus, their receptive fields spond to light with a slow hyperpolar- are very narrow. Parallel Processing izing response, they report quite differ- An image continues to be broken The parallel sets of visual channels for ent image properties. Rods, detecting into component elements at the first ON (detecting light areas on dark dim light, usually respond to relatively synapses of the visual pathway, those backgrounds) and OFF (detecting dark slow changes. Cones, dealing with between photoreceptors and bipolar areas on light backgrounds) qualities bright signals, can detect rapid light cells. Different bipolar cells have differ- of an image are fundamental to our fluctuations. In both cases, photorecep- ent types of receptors for the neuro- seeing. Vertebrate vision depends on tors begin the process of decomposing transmitter glutamate, allowing the perceiving the between im- ages and their backgrounds. For ex- pigment ample, we read black letters against a epithelium white background using the OFF chan- nels that start in the retina. Parallel rods bipolar channels transmit inputs to ganglion cells. Early in development cones the architecture of the inner plexiform layer, full of synapses between bipolar outer plexiform and ganglion cells, shows that synaptic layer connections become segregated in dis- tinct, parallel pathways. Connections horizontal occur between ON bipolar cells and cells ON ganglion cells and also between bipolar OFF bipolar cells and OFF ganglion cells cells in demarcated portions of the in- ner plexiform layer. amacrine If the retina were simply to transmit cells opposite-contrast images directly from inner the photoreceptors to the brain, the re- plexiform sulting vision would probably be layer coarse-grained and blurry. Further pro- ganglion cessing in the retina defines precise cells edges to images and allows us to focus on fine details. The honing of the im- nerve fiber age starts at the first synaptic level in layer the retina, where horizontal cells re- Figure 3. Cells in the retina are arrayed in discrete layers. The photoreceptors are at the top of ceive input from cones. Each horizontal this rendering, close to the pigment epithelium. The bodies of horizontal cells and bipolar cells cell actually receives input from many compose the . Amacrine cells lie close to ganglion cells near the surface of cones, so its collection area or receptive the retina. -to-dendrite neural connections make up the plexiform layers separating rows field is large. Horizontal cells’ receptive of cell bodies. fields become even broader because © 2003 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. 30 American Scientist, Volume 91 N disc

surface C rhodopsin

retinal 11-cis retinal 11-trans

light O

O

Figure 4. Cone photoreceptors from a monkey are stained with a fluorescent green dye (left). When the outer segments of cones or rods are mag- nified further, stacked membrane disks are visible inside (middle). The disks are studded with thousands of rhodopsin complexes. Each rhodopsin consists of a membrane-traversing protein with a retinal molecule embedded in its core (right). When exposed to light, one of the bonds in the retinal molecule rotates, changing the shape of the protein (lower right). (Middle photograph courtesy of Carlos Rozas.) their plasma membranes fuse with cone photoreceptor. This complicated cir- these cells in the organization of visual those of neighboring horizontal cells at cuit from horizontal cell to cone to bipo- messages. Horizontal cells respond to gap junctions. The membrane potentials lar cells is still a subject of hot debate in more than the photoreceptors that link of a whole sheet of cells become the the community of retina scientists. to them. Feedback signals from the inner same; consequently, horizontal cells re- Horizontal-cell function has occupied plexiform layer influence horizontal-cell spond to light over a very large area. many vision scientists for decades, and activity as well. These feedback signals Meanwhile, a single bipolar cell receives much is now known about the role of are transmitted via substances such as input from a handful of cones and thus has a medium-size . human retina turtle retina Whereas a single bipolar cell with its OFF or ON light response would carry a fairly blurry response to its ganglion cell, horizontal cells add an opponent signal that is spatially constrictive, giv- visual streak ing the bipolar cell what is known as a center surround organization (Figure 9). fovea optic The bipolar center signals either ON or nerve OFF, and the horizontal cells add an OFF or ON surround signal, by one of optic nerve two means. The horizontal cells can ei- ther signal the bipolar cell or feed infor- mation back to the cone photoreceptors themselves, which then feed forward information to the bipolar cells the Figure 5. An ophthalmologist’s view of the human retina (left) shows the optic nerve head, cones contact. Feedback to the cones is from which blood vessels radiate to nourish every part of the tissue, as well as the fovea, now proposed to occur by means of an which is where images focus most directly and is specialized for sharp daylight vision. The unusual electrical consisting of fovea is densely packed with more than half of the human cone photoreceptors. The turtle reti- half a ; these hemi gap junc- na (right) has no blood vessels radiating from the optic nerve and no fovea. Instead, it has a vis- tions are thought to change the ionic en- ual streak, a region of specialized cells running horizontally above the optic nerve, which can vironment across the membrane of the detect fleeting movements and orient those movements relative to the horizon. © 2003 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. 2003 January–February 31 ter and surround even further than the horizontal-cell input does. In human retinas, two basic types of ganglion cells—ON center and OFF center— form the major output of the retina to the visual centers in the brain (Figure 10, left). ON-center ganglion cells are ac- polarization tivated when a spot of light falls in the center of their receptive field and are green flash inactivated when light falls on the field’s periphery. OFF-center ganglion time cells react in the opposite way: Their ac- tivity increases when the periphery of their receptive field is lit and decreases receptive field when light falls on the center of the field. (The receptive fields of ganglion cells are modeled as the difference be- tween Gaussian distributions, giving them a so-called Mexican-hat shape.) In contrast to the rest of the retina, the human fovea contains midget ganglion cells, which have minute dendritic trees

hyperpolarization connected in a one-to-one ratio with midget bipolar cells (Figure 10, right). The channel from midget bipolar to midget ganglion cell carries information from a Figure 6. A single green-sensitive cone photoreceptor responds to the presence of green light single cone, thus relaying a point-to- by becoming hyperpolarized; that is, the membrane’s electrical potential becomes more nega- point image from the fovea to the brain. tive. The hyperpolarization lasts as long as the light flash (top right). The cone only responds to Each red or green cone in the central light immediately directed to it, so its receptive field is very narrow (bottom right). fovea connects to two midget ganglion cells, so at all times each cone can either , nitric oxide and retinoic even make the bipolar cells’ response transmit a dark-on-light (OFF) signal or a acid. The result is that horizontal cells color-coded, all apparently through light-on-dark (ON) message. The mes- modulate the photoreceptor signal un- feedback circuits to the cones. sage that goes to the brain carries both der different lighting conditions—al- The ganglion cells have a receptive spatial and spectral information of the lowing signaling to become less sensi- field organized as concentric circles. finest resolution. tive in bright light and more sensitive The amacrine-cell circuitry in the inner Messages from blue cones are not in dim light—as well as shaping the re- plexiform layer conveys additional in- processed in the same way as from red ceptive field of the bipolar cells, as we formation to the ganglion cell, possibly and green cones for some reason, possi- have seen. The horizontal cells can sharpening the boundary between cen- bly because the blue system is older in evolutionary terms. Blue cones are abcfound in the retinas of most species. The typical mammalian retina also has green cones; primates have the addi- tional red cones. Blue cones transmit in- rod cones formation through a special blue cone bipolar cell to a different type of gan- glion cell, which can carry both a blue inhibitory inhibitory excitatory ON and a yellow OFF response. glutamate glutamate glutamate Electrical recordings show that sev- receptor receptor receptor eral types of ganglion cells do not have ON ON OFF concentric organization, especially in bipolar bipolar bipolar animals whose eyes lack a fovea. This cell cell cell includes most nonmammalian species glutamate glutamate and mammalian species that have reti- nas with visual streaks. Compared with species with foveas, the species with visual streaks do even more im- Figure 7. Photoreceptors transmit information to bipolar cells using the molecule glutamate, but different bipolar cells respond differently to the presence of the molecule; some fire in re- age processing in the retina itself be- sponse, whereas others cease firing, depending on the kind of glutamate receptor on their sur- fore sending a message to the brain; face. ON bipolar cells have a depolarizing receptive field (a, b); OFF cells have a hyperpolar- their retinas can immediately synthe- izing receptive field (c). Contrary to what one might expect, photoreceptors stop releasing size information about image motion glutamate when stimulated by light, in turn causing ON bipolar cells to release glutamate. and direction of motion. © 2003 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. 32 American Scientist, Volume 91 Building Images with Amacrine Cells There is more to understand about the messages ganglion cells receive before they transmit a signal to the brain. For that, it is important to appreciate the organization of the inner plexiform lay- er, where 22 or more different types of amacrine cells make synaptic connec- tions with about 20 different types of ganglion cells. It was already clear from Cajal’s de-

scription in the 19th century that hyperpolarization amacrine-, ganglion- and bipolar-cell dendrites and were organized into distinct layers; Cajal himself divid- ed the inner plexiform layer into five strata. But what sorts of synapses were Figure 8. Photomicrograph of a retina shows the elongated cone photoreceptors and the hor- formed among the tangle of intermesh- izontal and bipolar cells to which they connect (left). The horizontal cells are stained yellow; ing processes and what this organiza- the bipolar and amacrine cells lie below them, stained green and red. Horizontal cells modu- tion meant were not immediately ap- late the responses of photoreceptors and bipolar cells. The receptive fields of horizontal cells parent. Electron microscopy helped to are very wide (right) because of electrical coupling among the cells. unravel this neurocircuitry. Now the interconnections of nine types of bipo- in a direct pipeline to bipolar cells to ner plexiform layer and create elegant lar cells, 14 types of amacrine cells and ganglion cells, the bipolar cells that re- meshworks of dendrites. Usually, they eight types of ganglion cells are under- ceive input from rods do not synapse emit GABA as a neurotransmitter. stood quite well. We can say we are with ganglion cells directly. The bipolar Sometimes they connect to neighbor- half way to the goal of understanding cells connected to rods are all of one ing amacrine cells by gap junctions, in- the neural interplay between all the type, solely transmitting an ON signal, creasing their sphere of influence and nerve cells in the retina. and use the AII and A17 amacrine cells the speed at which signals transmit Much is now known about what as intermediaries to get signals to gan- across large areas of retina. types of neurotransmitters different glion cells. The small-field AII cell col- Most GABA-releasing amacrine amacrine cells contain and about the lects from about 30 rod-connected cells also release at least one other organization of receptors at the differ- bipolar cells and transmits a depolariz- neuroactive substance. The secondary ent synapses. Amacrine cells are about ing message both to ON (light-detect- equally divided between those that use ing) cone bipolar cells and to their ON and those that use GABA ganglion cells and to OFF cone bipolar cones (gamma-aminobutyric acid) neuro- cells and OFF ganglion cells (Figure 11). transmitters. It is as if the AII cells developed in the Glycinergic amacrine cells are usu- rod-dominated parts of the retina as an ally “small field.” Their processes can afterthought to the cone-to-ganglion spread vertically across several strata cell architecture and now takes advan- within the inner plexiform layer, but tage of the preexisting cone pathway they extend relatively short distances circuitry. horizontally. Glycinergic amacrine cells At the same time, the A17 amacrine receive information from bipolar cells cell collects rod messages from thou- and transmit information to ganglion sands of rod-connected bipolar cells. It horizontal gap cells and to other bipolar and amacrine somehow amplifies and modulates the cells junctions cells. Some glycinergic amacrine cells information from the rod bipolar cells provide interconnections between ON to transmit to the AII cells, but how it and OFF systems of bipolar and gan- does this is not completely understood. bipolar cell glion cells. The most famous of these In any case, the rod pathway with its center surround is called the AII cell; the AII and a series of convergent and then diver- GABA-releasing called gent intermediary neurons is clearly A17 are pivotal in the circuitry of rod- well designed to collect and amplify based, dim-light vision in the mam- scattered vestiges of light for twilight malian retina. These cells aren’t found and . in mammalian species that are active Wide-field amacrine cells sometimes Figure 9. Horizontal cells accumulate informa- solely in daylight and have very few stretch horizontally across the inner tion from a wide field of cones and influence rods—for example, squirrels. plexiform layer for hundreds of mi- the signals bipolar cells transmit by adding an In the earlier discussion of ON and crons and interact with hundreds of opponent surround signal to their receptive OFF channels emanating from cones, I bipolar cells and many ganglion cells. fields. The horizontal cells influence bipolar neglected to talk about the channels Such amacrines are usually confined to cells either directly or by feeding back infor- from rod cells. Whereas cones connect one of the five different strata of the in- mation to the cones—probably both. © 2003 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. 2003 January–February 33 in fovea

ON ON ON OFF OFF OFF ON OFF

bipolar horizontal midget cells cells bipolar cells

midget ganglion cells ganglion cells ON- OFF- center center ON OFF

to to brain to brain brain hyperpolarization hyperpolarization depolarization depolarization

ON center, OFF center, ON center, OFF center, OFF surround ON surround OFF surround ON surround

Figure 10. Human retinas have two types of ganglion cells—ON-center and OFF-center. ON-center ganglion cells are activated when a spot of light falls in the center of their receptive fields, whereas OFF-center ganglion cells fire in response to light falling on their fields’ periphery leav- ing their center dark. Horizontal cells convey antagonistic surround signals to bipolar cells and thence to ganglion cells. Ganglion cells have re- ceptive fields with a Mexican-hat shape, reflecting their integration of opposing information about centers and surrounds. This kind of pro- cessing helps sharpen the boundaries of images. In the fovea (right), ganglion cells have much narrower receptive fields; in fact, each carries information from a single cone. A cone feeds information to two of these midget ganglion cells; at all times each foveal cone transmits either an ON or an OFF signal to the brain. This signal also carries a color message regarding the type of cone (red or green) it comes from.

rods cones

AII amacrine ON ON cell ON OFF

bipolar cells

gap junction

ganglion ON cells OFF

Figure 11. AII amacrine cells play an important role in transmitting information from rod photoreceptors to ganglion cells. The amacrine cells collect messages from many rod-connected bipolar cells, allowing the perception of very dim light. The amacrine cells feed information directly to OFF ganglion cells. They also co-opt the ON cone bipolar-to-ganglion cell architecture by means of gap junctions. © 2003 Sigma Xi, The Scientific Research Society. Reproduction 34 American Scientist, Volume 91 with permission only. Contact [email protected]. example, the major neural pathway from the rods depends on direct elec- trical connections. Some other fast-act- ing signals pass from amacrine cells into ganglion cells at gap junctions. Neuromodulators change the milieu of the circuits but act from a dis- tance by diffusion rather than at closely apposed synapses. Again, this is a sur- prising concept compared to the previ- ous view that all neural interactions take place via neurotransmitters at spe- cialized isolated patches of membrane apposition—that is, synapses. The most recent surprise has been that a previously unknown ganglion cell type appears to function as a giant photore- ceptor itself, without needing input from rods or cones. This ganglion’s cell membrane contains light-reactive mol- Figure 12. Photographs highlighting two different kinds of amacrine cells show their dense ecules known as . Given network of dendrites and axons, which send information to various types of cells. One is such unexpected findings, it appears stained for its neuromodulator, dopamine (left), and the other for its neurotransmitter, acetyl- that there may still be much more to choline (right). Many amacrine cells are electrically coupled by gap junctions, creating a mas- learn about how the retina works. sive sheet of cells able to transmit information quickly and in unison. Bibliography substances are usually neuromodulators sulting uncoupling of the AII cells Dowling, J. E. 1987. The Retina: An Approach- rather than fast-acting neurotransmit- makes the effective field of influence of able Part of the Brain. Cambridge, Mass.: ters. The substances include peptides— the rod-system amacrine cells much Belknap Press. “substance P,” somatostatin, vasointesti- less significant in lighter conditions. Hattar, S., H.-W. Liao, M. Takao, D. M. Berson and K.-W Yau. 2002. -containing nal peptide and cholecystokinin—as Similarly in bright light conditions, an- retinal ganglion cells: Architecture, projec- well as the more familiar biomolecules other wide-field amacrine cell releases tions, and intrinsic photosensitivity. Science , dopamine, acetylcholine, nitric oxide to uncouple the AII cell 295:1065–1070. adenosine and nitric oxide. A variety of from the cone-bipolar system. All this Kolb, H. and E. V. Famiglietti. 1974. Rod and receptors have been found on ganglion removes the interference of the large- cone pathways in the inner plexiform layer and bipolar cells—for example, recep- field rod pathway from the narrow- of the cat retina. Science 186:47–49. Kolb, H. , R. Nelson, P. Ahnelt and N. Cuenca. tors for peptides, nicotine and mus- field cone pathways. 2001. Cellular organization of the vertebrate carine (mushroom toxin) in addition to The above broad sketch of retinal retina. In Concepts and Challenges in Retinal different forms of GABA receptors—in- circuitry suggests that the retina is re- : A Tribute to John E. Dowling, pp. dicating that amacrine cells are releasing markably complex. As vision research 3–26, ed. H. Kolb, H. Ripps and S. Wu. Am- such agents. Most of these neuro- advances, the retina seems to take on sterdam: Elsevier Press. modulators are not active at convention- an increasingly active role in percep- Kolb, H., E. Fernandez and R. Nelson. 2002. Web- vision: The Organization of the Retina and Visual al synapses; their release is thought to tion. Although we do not fully under- System. http://www.webvision.med.utah.edu influence neurons even at a distance by stand the neural code that the gan- Nelson, R., E. V. Famiglietti and H. Kolb. 1978. diffusion. Such neuromodulators appar- glion-cell axons send as trains of spikes Intracellular staining reveals different lev- ently influence the retinal circuitry un- into the brain, we are coming close to els of stratification for on-center and off-cen- der changing light conditions or even understanding how ensembles of gan- ter ganglion cells in the cat retina. Journal of cause retinal activity to reflect the differ- glion cells respond differently to as- Neurophysiology 41:427–483. Rodieck, R. W. 1998. The First Steps in Seeing. ent times of day in the circadian clock. pects of the visual scene and how fields Sunderland, Mass.: Sinauer Associates. A specialized amacrine cell releases of influence on particular ganglion dopamine when the retina is stimulat- cells are constructed. Much of the con- ed with intermittent flashing light. struction of the visual images does Dopamine causes the gap junctions seem to take place in the retina itself, among horizontal cells to become un- although the final perception of sight Links to Internet resources for further coupled, reducing the size of their re- is indisputably done in the brain. exploration of “How the Retina ceptive fields. Furthermore, the neuro- Given how much is now known, it Works” are available on the American transmitter affects the glutamate might be fair to ask, are we finished Scientist Web site: receptor on horizontal cells so that the with the retina, or are there more sur- amplitude of the light response de- prises on the horizon? Earlier surprises http://www.americanscientist.org/ clines. Again in the inner plexiform included finding that much of the in- articles/03articles/kolb.html layer, dopamine closes gap junctions, formation transfer depended on elec- this time the ones that link AII ama- trical connections among cells rather crine cells in large networks. The re- than standard chemical synapses. For © 2003 Sigma Xi, The Scientific Research Society. Reproduction with permission only. Contact [email protected]. 2003 January–February 35