Ординатура / Офтальмология / Английские материалы / The Retina and its Disorders_Besharse, Bok_2011

Further Reading

Borghuis, B. G., Sterling, P., and Smith, R. G. (2009). Loss of sensitivity in an analog neural circuit. Journal of Neuroscience 29: 3045–3058.

Carandini, M., Demb, J. B., Mante, V., et al. (2005). Do we know what the early visual system does? Journal of Neuroscience 25: 10577–10597.

Chichilnisky, E. J. (2001). A simple white noise analysis of neuronal light responses. Network 12: 199–213.

Dacey, D. M., Peterson, B. B., Robinson, F. R., and Gamlin, P. D. (2003). Fireworks in the primate retina: In vitro photodynamics reveals diverse LGN-projecting ganglion cell types. Neuron 37: 15–27.

Dhingra, N. K., Kao, Y. H., Sterling, P., and Smith, R. G. (2003). Contrast threshold of a brisk-transient ganglion cell in vitro. Journal of Neurophysiology 89: 2360–2369.

Enroth-Cugell, C. and Robson, J. G. (1966). The contrast sensitivity of retinal ganglion cells of the cat. Journal of Physiology 187: 517–552.

Field, G. D. and Chichilnisky, E. J. (2007). Information processing in the primate retina: Circuitry and coding. Annual Review of Neuroscience 30: 1–30.

Geisler, W. S. (1989). Sequential ideal-observer analysis of visual discriminations. Psychological Review 96: 267–314.

Merigan, W. H. and Maunsell, J. H. R. (1993). How parallel are the primate visual pathways? Annual Review of Neuroscience 16: 369–402.

Rose, A. (1973). Vision: Human and Electronic. New York: Plenum Press.

Sterling, P. and Demb, J. B. (2004). Retina. In: Shephard, G. (ed.)

Synaptic Organization of the Brain, 5th edn., pp. 217–269. New York: Oxford University Press.

Troy, J. B. and Enroth-Cugell, C. (1993). X and Y ganglion cells inform the cat’s brain about contrast in the retinal image. Experimental Brain Research 93: 383–390.

Wandell, B. A. (1995). Foundations of Vision. Sunderland: MA: Sinauer. Walraven, J., Enroth-Cugell, C., Hood, D. C., MacLeod, D. I. A., and

Schnapf, J. L. (1990). The control of visual sensitivity: Receptoral and postreceptoral processes. In: Spillman, L. and Werner, J. (eds.) The Neurophysiological Foundations of Visual Perception, pp. 53–101.

New York: Academic Press.

Wa¨ssle, H. (2004). Parallel processing in the mammalian retina. Nature Reviews. Neuroscience 5: 747–757.

Watson, A. B., Barlow, H. B., and Robson, J. G. (1983). What does the eye see best? Nature 302: 419–422.

Glossary

Accessory optic nuclei – A series of small nuclei in the rostral midbrain, near where the optic tract enters the lateral geniculate nucleus. They receive inputs from motion-sensitive ganglion cells and project to the vestibular nuclei, triggering optokinetic movements in response to movement of the visual world across the retina. This system is very important for animals without foveae, but is poorly developed in humans.

Optokinetic nystagmus – The repeated reflexive responses of the eyes to ongoing large-scale movements of the visual scene.

Patch-clamp recording – A sensitive electrophysiological recording technique that permits the measurement of ionic currents flowing through individual ion channels. It uses a glass micropipette that has an open-tip diameter of about 1 mm. The micropipette tip is sealed onto the cell surface, enclosing a membrane surface area or patch that often contains only a few ion channels. Several variations of this technique are commonly applied.

Spatially offset inhibition – An inhibitory synaptic input from the receptive field surround that is asymmetrically offset to one direction.

Two-flash apparent motion stimulation – A visual stimulation paradigm, in which two nearby spots of light are flashed in rapid succession to simulate the motion of a light spot.

Detecting the direction of image movement is an essential task of the visual system. Neurons in many parts of the visual system show directional sensitivity to image motion. The initial computation of movement direction is accomplished in the retina. In the early 1960s, Barlow and co-workers discovered that a subset of output neurons in the rabbit retina responds vigorously to an image moving across its receptive fields in a particular (preferred) direction, but gives little or no response to the same image moving in the opposite (null) direction (Figure 1). These retinal neurons, termed directionselective ganglion cells (DSGCs), display a directional preference that is independent of the nature of the image, such as contrast, size, and complexity. They are specialized in processing visual information regarding motion and motion direction.

Physiological Functions of DSGCs

In rabbit, a species for which retinal direction selectivity is best characterized, two types of DSGCs have been found: the ON type, which responds to the onset of a small spot of light flashed in the center of the cell’s receptive field, and the ON–OFF type, which responds to both the onset and the offset of such a flash. ON DSGCs project their axons to the accessory optic system. They are believed to be involved in the feedback mechanism that stabilizes a moving image on the retina, for example, during the smooth tracking movements of the eyes. These cells respond best to slow image movements ( 0.3 s–1) and contribute significantly to the control of optokinetic nystagmus over the range of stimulus velocities that produce the most complete minimization of image motion on the retina. ON DSGCs are divided into three subtypes, distinguished by their preferred directions pointed roughly toward the anterior, superior, and inferior retina, respectively. Each of these three preferred directions is thought to correspond to a component of the head rotation that activates one of the three pairs of semicircular canals in the inner ears, suggesting that these cells may also detect the slippage of a visual image on the retina during head rotation and provide an error signal that tells the visual servo-system to compensate the difference between head rotation and eye rotation.

ON–OFF DSGCs, on the other hand, project to the superior colliculus and the lateral geniculate nucleus. They are further categorized into four subtypes, characterized by their preferred directions which, respectively, point roughly toward the four cardinal directions in the retina: superior, inferior, anterior, and posterior. It has been suggested that these four directions may correspond to the directions in which the eye is rotated by the four extraocular rectus muscles, indicating that ON–OFF DSGCs are also involved in the feedback mechanism that controls eye movement. However, unlike the ON type, ON–OFF DSGCs give largest responses to fast movements ( 10 s–1 or faster) and respond poorly to slow movements. Their contribution to image stabilization during the slow phase of optokinetic nystagmus may be significant only at stimulus velocities exceeding3 s–1. The fact that ON–OFF DSGCs project to the lateral geniculate nucleus in addition to the superior colliculus suggests that these cells may also process directional information of object movement for visual perception. However, the exact physiological functions of ON–OFF DSGCs remain to be understood.

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Synaptic Circuitry of DSGCs

As direction selectivity in the retina represents a fundamental form of information processing, it has been regarded as a model system for understanding neuronal computation in the brain. In their 1965 work, Barlow and Levick first suggested that the direction selectivity of ganglion cells is built from sequence-discriminating subunits. The primary mechanism for this discrimination was thought to result from a spatially offset lateral inhibition, which vetoes responses to sequences corresponding to stimulus movement in the null direction. Pharmacological experiments by Daw and colleagues subsequently found that gamma aminobutyric acid (GABA) receptor antagonists block direction selectivity by bringing out strong responses of DSGCs to stimulus movement in the null direction, suggesting that the spatially offset inhibition is mediated by GABA. Direct measurement of the inhibitory inputs to ON–OFF DSGCs became possible in the early 2000s, when whole-cell patch-clamp recordings were made successfully from these cells in the wholemount rabbit retina by several labs. Fried and co-workers showed that the inhibitory input to ON–OFF DSGCs is larger during stimulus movement in the null direction than that in the preferred direction, and that the inhibitory input arrives ahead of the excitatory input when the stimulus moves in the null, but not in the preferred

direction. The spatial extent of the inhibitory input measured by whole-cell patch clamp is offset from the ON–OFF DSGC dendritic field toward the null direction. The excitatory current input to an ON–OFF DSGC is also directionally asymmetric: larger for preferred direction movement than for null direction movement. Similar results were also obtained from ON DSGCs in the mouse retina. These findings establish that the synaptic inputs to a DSGC are already directionally asymmetric.

An important clue to the origin of major synaptic inputs to DSGCs comes from the anatomical structure of these cells. DSGCs have a distinctive morphology, characterized by the looping dendritic branches (Figure 2). The dendritic stratification pattern of DSGCs follows the general rule of segregation between the ON and OFF channels in the inner plexiform layer (IPL) of the retina. Thus, ON DSGCs arborize only in the proximal half (ON sublamina) of the IPL, whereas ON–OFF DSGCs arborize in both the proximal and the distal half (OFF sublamina). Both the ON and OFF arborizations stratify narrowly in the IPL, juxtaposing the two narrow cholinergic strata, suggesting that DSGCs receive synaptic inputs from the relatively small number of bipolar and amacrine cell subtypes that terminate specifically in these strata. In particular, cholinergic amacrine cells, which are the only cholinergic cells in the mammalian retina, are expected to provide a significant amount of lateral input to DSGCs. Cholinergic amacrine

Figure 3 Dendritic morphology of starburst amacrine cell. Fluorescence micrograph of a SAC, with its soma located in the ganglion cell layer in a postnatal day 18 retina of a rabbit. The cell has a radially symmetric dendritic tree and a polar asymmetric synaptic structure. The input synapses from bipolar cell are distributed over the whole dendritic tree, but the output synapses are localized in the distal varicose zone, where synaptic vesicles are concentrated. Unpublished micrograph provided by Lee

S and Zhou ZJ.

cells are also known as starburst amacrine cells (SACs; Figure 3). They exist as two mirror-symmetric populations across the IPL. They have four to five primary dendrites, each branching out regularly into secondary and tertiary

processes, with numerous varicosities imbedded in the distal dendritic zone. The dendritic tree of a SAC emanates from the soma with a nearly perfect radial symmetry, rendering the cell a starburst appearance and hence its popular name. The processes of neighboring SACs overlap significantly and form honeycomb-shaped plexuses which co-fasciculate extensively with the looping dendrites of DSGCs, suggesting intimate synaptic interactions between the two cell types. Indeed, direct synapses from SACs to ON–OFF DSGCs have been observed at the electron microscopic level.

The neurochemical significance of the synapses between SACs and DSGCs became apparent when SACs were found to synthesize and release both acetylcholine (ACh) and GABA, a property that also rendered SACs the first known exception to Dale’s principle of one neuron releases one fast neurotransmitter. The GABAergic nature of cholinergic amacrine cells suggests that these cells may provide the crucial, spatially offset GABAergic inhibition to DSGCs, an idea that has been tested and debated extensively in the literature. The co-release of ACh and GABA by SACs also raises the possibility that these two neurotransmitters may be used by SACs in a complimentary manner to enhance the sensitivity of DGSCs to motion and motion direction.

The first functional evidence for a key role of SACs in direction selectivity came from the finding that ablation of SACs by immunotoxins and neurotoxins results in an apparent elimination of the directional discrimination of DSGCs in the mouse retina, as well as a loss of optokinetic nystagmus. This finding demonstrates a critical link not only between SACs and direction selectivity, but also between direction selectivity and optokinetic

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Figure 4 Synaptic circuit of ON–OFF direction selective ganglion cells. ON–OFF DSGCs receive GABAergic inhibitory inputs only from starburst amacrine cell dendrites that point in the null direction, but not in the preferred direction. A single SAC (shown in black) can provide null-direction inhibition to all four subtypes of ON–OFF DSGCs with preferred directions along four orthogonal directions (shown in different colors). For simplicity, only the circuitry in the ON sublamina is shown. Adapted from Taylor, W. R. and Vaney, D. I. (2003). New directions in retinal research. Trends in Neurosciences 26(7): 379–385.

nystagmus. Dual patch-clamp recordings from SAC–DSGC pairs in the rabbit retina subsequently demonstrated that DSGCs receive direct GABAergic synaptic inputs from SACs, and that such inputs come only from SACs located on the null side, but not the preferred side of the DSGC. This result establishes that SACs exert a spatially offset GABAergic inhibition on DSGCs through directionally asymmetric hardwiring between SACs and DSGCs, a landmark finding that forms the basis of the current model of the synaptic circuitry of DSGCs (Figure 4).

Direction-Selective Responses in SAC

Processes

For the asymmetric wiring model of direction selectivity shown in Figure 4 to work, the release of GABA from each branch of a SAC must also be directionally selective: larger during a null-direction movement and smaller during a preferred-direction movement. Otherwise, the SAC dendrites that synapse on a DSGC from the null direction would still inhibit the DSGC when an image moves to the DSGC receptive center along the preferred direction, even though such an inhibitory input may not precede the glutamatergic excitatory input from bipolar cells. Experiments using apparent motion stimulation also show that the GABAergic input to a DSGC (from SACs on the null side) is strongly suppressed by two-spot flashes that simulate a preferred-direction movement, indicating that GABA release from SAC dendrites is directionally selective. This

result suggests that a critical component of the directionselective mechanism must reside upstream from DSGCs and in SACs.

How does a morphologically symmetric cell like the starburst produce the functional asymmetry required for direction-selective GABA release? A close anatomical examination of the SAC tells us that, despite the striking radial symmetry in the dendritic tree, the synaptic structure of the cell has a profound polar asymmetry. Input synapses on starburst dendrites distribute more or less uniformly along the entire dendritic length, whereas output synapses are localized in the distal varicose zones, where synaptic vesicles are concentrated (Figure 3). The distal varicose zones are believed to be electrotonically semi-isolated, due to the thin diameter of the dendrites and a heavy expression of KV3 voltage-gated potassium channels on the proximal dendrites. This polar asymmetry in input–output relation, combined with the short electrotonic length of the dendrites, would enable the distal dendrites of a SAC to process directional signals independently, with a preference to centrifugal stimulus movement, as predicted by computational models. In an elegant two-photon Ca2þ-imaging experiment, Euler and co-workers showed that distal starburst dendrites respond to spot illumination with intracellular Ca2þ transients that are restricted to distal dendrites. Importantly, these local Ca2þ responses tended to be directionally selective: stronger for centrifugal than for centripetal stimulus movement.

Two-flash apparent motion experiments further show that the direction selectivity in distal starburst dendrites involves both centrifugal excitation and centripetal inhibition. The underlying mechanism may involve both cellautonomous properties and synaptic interactions at SAC dendrites. Cell-autonomous properties, such as nonlinear interactions between the activation of voltage-gated calcium channels and a gradient in membrane potential along the SAC dendrites, may contribute to an enhanced response of the distal dendrites to centrifugal image movement. On the other hand, synaptic interactions, particularly GABAergic inhibition from the receptive field surround, play a key role in centripetal inhibition. Dual patch-clamp recording experiments found that neighboring SACs inhibit each other through reciprocal GABAergic synapses. Zhou and Lee proposed that the synaptic mechanism for direction-selective release of GABA in distal starburst dendrites is built primarily from a classic centersurround receptive field structure. Synaptic inputs to the receptive field center are dominated by the glutamatergic input from bipolar cells, whereas synaptic inputs from the receptive field surround are dominated by the direct GABAergic input from neighboring SACs. Such a concentric receptive field structure would normally be directionally symmetric for a neuron that makes an integrative output decision at the soma or axon hillock. However, since the output decisions of a SAC are made

independently in individual distal dendrites, such a concentric center-surround receptive field structure would produce a profound directional asymmetry at distal dendrites, where synaptic inputs received during centrifugal stimulus movement are dominated by excitation, but synaptic inputs received during centripetal stimulus movement are dominated by inhibition. This synaptic mechanism, together with an intrinsic mechanism that promotes centrifugal facilitation, would produce robust directionselective GABA release from SACs.

Integration of Multiple Cooperative Mechanisms for Direction Selectivity

The direction-selective circuit so far identified consists primarily of DSGCs, SACs, and subsets of bipolar cells, although other amacrine cell types may also participate in the regulation of DSGC receptive fields. Distinct mechanisms of direction selectivity work in concert at three different levels. First, at the DSGC level, direction selectivity is shaped largely by a spatially offset inhibition from SACs, whose distal dendrites release GABA in a direction-selective manner and make GABAergic synapses onto DSGCs asymmetrically from the null direction only. Direction selectivity of DSGCs is also enhanced by the directionally asymmetric excitatory inputs, which may contain both glutamatergic and cholinergic components. In addition, a postsynaptic mechanism, involving local signal computation and spike generation in DSGC dendrites, may further sharpen direction selectivity. Second, at the SAC level, direction selectivity is formed in the distal starburst dendrites by a profound polar asymmetry between centrifugal excitation and centripetal inhibition. GABAergic inhibition, mediated largely by reciprocal inhibition between SACs, plays a key role in suppressing SAC responses to centripetal stimulus motion. However, the nature of lateral synaptic interaction during centrifugal motion is currently unclear. A model based on differential expression of two different chloride transporters proposes that the excitability of GABAergic input changes as the image moves centrifugally or centripetally along a SAC dendrite. Further experiments are required to test directly the predictions of this model. In addition to synaptic interactions, intrinsic cellular properties also play an important role in shaping direction selectivity in SAC dendrites, predominantly by contributing to centrifugal facilitation. Third, at the bipolar cell level, a direction-selective release of glutamate is strongly implicated by the finding of asymmetric excitatory inputs to DSGCs, but the underlying mechanism remains a major missing piece of the puzzle. A key issue is whether local terminals of a bipolar cell axon can function independently and make selective synapses with the dendrites of specific subtypes of DSGCs. An intriguing possibility in

this regard is that SACs asymmetrically inhibit specific bipolar cell output synapses, which in turn synapse selectively on DSGCs in a spatially asymmetric manner.

While the critical GABAergic contribution of SACs to direction selectivity is well accepted, the cholinergic role of SACs remains elusive. Various models of cholinergic contributions to direction selectivity and motion sensitivity have been proposed over the years. However, the basic mode of nicotinic cholinergic action in the retina still remains obscure: Does ACh mediate fast neurotransmission at precise synaptic sites between SACs and DSGCs, or does it play a diffuse, paracrine role in modulating the activity of many ganglion cell types? More detailed experimental results are needed before it can be concluded as to how the release of ACh from SACs may enhance the sensitivity of DSGCs to image movement, whether cholinergic interactions enhance direction selectivity, how cholinergic synapses form a neural circuit, and how the cholinergic and GABAergic circuits of SACs interact with each other. Investigations into some of these questions are currently underway and may uncover additional levels of cooperation among synaptic mechanisms of motion and direction selectivity in the near future.

Concluding Remarks

Direction selectivity is a basic form of information processing produced by a relatively simple neuronal circuit in the inner retina. In order for this circuit to accomplish the robust computation required for detecting motion direction, multiple levels of cooperative mechanisms are integrated at each synapse. Such synaptic integration may represent an important feature of network computation in the central nervous system. From an anatomical point of view, the direction-selective circuit in the retina reveals a level of selectivity and precision in network organization that was previously unappreciated in most other parts of the central nervous system. Understanding the developmental mechanisms that control the establishment of the direction-selective circuit in the retina remains a challenging task of future investigation and will shed important light on the development of neuronal circuits in general.

Acknowledgments

This work is supported in part by grants from the National Eye Institute and Research to Prevent Blindness, Inc.

See also: GABA Receptors in the Retina; Information Processing: Amacrine Cells; Information Processing: Bipolar Cells; Information Processing: Ganglion Cells; Information Processing in the Retina; Morphology of Interneurons: Amacrine Cells.

Further Reading

Barlow, H. B. and Levick, W. R. (1965). The mechanism of directionally selective units in rabbit’s retina. Journal of Physiology 178(3): 477–504.

Barlow, H. B., Hill, R. M., and Levick, W. R. (1964). Retinal ganglion cells responding selectively to direction and speed of image motion in the rabbit. Journal of Physiology 173: 377–407.

Dacheux, R. F., Chimento, M. F., and Amthor, F. R. (2003). Synaptic input to the on–off directionally selective ganglion cell in the rabbit retina. Journal of Comparative Neurology 456(3): 267–278.

Demb, J. B. (2007). Cellular mechanisms for direction selectivity in the retina. Neuron 55(2): 179–186.

Euler, T., Detwiler, P. B., and Denk, W. (2002). Directionally selective calcium signals in dendrites of starburst amacrine cells. Nature 418 (6900): 845–852.

Famiglietti, E. V. (1991). Synaptic organization of starburst amacrine cells in rabbit retina: Analysis of serial thin sections by electron microscopy and graphic reconstruction. Journal of Comparative Neurology 309(1): 40–70.

Fried, S. I., Munch, T. A., and Werblin, F. S. (2002). Mechanisms and circuitry underlying directional selectivity in the retina. Nature 420(6914): 411–414.

Lee, S. and Zhou, Z. J. (2006). The synaptic mechanism of direction selectivity in distal processes of starburst amacrine cells. Neuron 51(6): 787–799.

Oyster, C. W., Takahashi, E., and Collewijn, H. (1972). Directionselective retinal ganglion cells and control of optokinetic nystagmus in the rabbit. Vision Research 12(2): 183–193.

Rodieck, R. W. (1998). The First Steps in Seeing. Sunderland, MA: Sinauer.

Tauchi, M. and Masland, R. H. (1984). The shape and arrangement of the cholinergic neurons in the rabbit retina. Proceedings of the Royal Society of London. Series B. Biological Sciences 223(1230):

101–119.

Taylor, W. R. and Vaney, D. I. (2003). New directions in retinal research.

Trends in Neurosciences 26(7): 379–385.

Vaney, D. I. (1990). The mosaic of amacrine cells in the mammalian retina. Progress in Retinal Research 9: 49–100.

Wyatt, H. J. and Day, N. W. (1976). Specific effects of neurotransmitter antagonists on ganglion cells in rabbit retina. Science 191(4223): 204–205.

Yoshida, K., Watanabe, D., Ishikane, H., et al. (2001). A key role of starburst amacrine cells in originating retinal directional selectivity and optokinetic eye movement. Neuron 30(3): 771–780.

Glossary

Excitation – The synaptic input to a cell that serves to depolarize and activate it.

Inhibition – The synaptic input to a cell that serves to hyperpolarize and suppress it.

Receptive field – For retinal cells, this refers to a region in the visual environment in which the presence of a visual stimulus will influence the activity of the neuron.

The eye is often compared to a camera, in which the retina plays the role of the film. However, this analogy does not do justice to the remarkable imageand information-processing capabilities of the retina. The roles that horizontal cells, bipolar cells, and amacrine cells play in the information processing in the retina have been discussed elsewhere in the encyclopedia. All their activity merges into the output cells of the retina, the ganglion cells. These cells form a sort of bottleneck through which all the information has to pass, which is destined to reach higher visual centers in the brain.

Ganglion Cell Types

The signals leaving the retina are transmitted by several channels, each channel carrying information about different features of the visual world. Each channel is embodied by a certain type of ganglion cell. It is still controversial how many different types of ganglion cells exist, but 20 should be a reasonable upper limit. Two ganglion cells are considered to belong to the same type if they share a defined set of properties, including morphological, physiological, and genetic properties. However, it is not trivial to define what such characterizing properties should be. Too fine a distinction would artificially separate ganglion cells into different types, even though they might belong to the same type, while a course classification will not do justice to the rich diversity of image-processing capabilities of the retina. For the purpose of this article, the term ganglion cell type will be loosely and pragmatically defined as the population of ganglion cells extracting the same features from the visual world and therefore performing the same function. Later in this article, we describe some specific examples of ganglion cell types and the visual features that activate them. First, however, we discuss some general principles of ganglion cell processing.

Principles of Ganglion Cell Processing

Neural activity in the retina is unusual in the central nervous system as most retinal neurons are analog: they do not fire action potentials; instead, transmitter release is a continuous function of membrane voltage. Ganglion cells are different; they use action potentials to transmit their signals along their axons which form the optic nerve. These cells integrate excitatory input from bipolar cells and inhibitory input from amacrine cells. It is the precise temporal and spatial integration of these inputs that leads to the final spiking output of the ganglion cells. It will become clear from the examples below that it is the inhibitory activity of the amacrine cells that creates most of the specificity in ganglion cell responses. Bipolar cells serve to set up a range of permissive stimuli, that is, the set of stimuli that a ganglion cell could, in principle, respond to. This stimulus space is then strongly restricted by the activity of the inhibitory amacrine cells, resulting in the specific responses of ganglion cell types.

Temporal Processing

Ganglion cells show diverse responses to step changes of light (Figure 1(a)). Generally, responses can be divided into ON (activated by increases of light intensity), OFF (activated by decreases of light intensity), and ON–OFF (activated by both increases and decreases of light intensity). The ganglion cells expressing these responses are accordingly termed ON cells, OFF cells, and ON–OFF cells. Within each of these classes, one can find cell types with transient or sustained responses. In addition, different cells have different latencies from stimulus onset until the time of the first spike. For some cell types, Gollisch and Meister demonstrated that the relative spike latency can code for the stimulus intensity (Figure 1(b)).

The different temporal response characteristics of ganglion cells are correlated with the level of stratification of ganglion cell dendrites. The dendrites of ON ganglion cells stratify in the inner half of the inner plexiform layer (sublamina b, close to the cell bodies of the ganglion cells), while the dendrites of the OFF ganglion cells stratify in outer half (sublamina a, toward the bipolar cells). The transient cells tend to stratify toward the center of the inner plexiform layer (IPL), while the sustained cells send their dendrites to the two borders of the IPL.

Stimulus

Figure 1 Temporal response characteristics of ganglion cells. (a) Different types of ganglion cells respond differently to the onset of a bright stimulus in the receptive field. ON cells respond at the onset of the stimulus; OFF cells respond at the offset; and ON–OFF cells respond at the both the onand offset. Within these cell classes, one can find transient and sustained types of responses. (b) The latency of responses of some cell types indicates the intensity of the stimulus. Left: The stimulus image was presented to the retina multiple times at different locations, so that the recorded ganglion cell was located at the positions indicated by the dots. Middle: Spiking responses for the column of recording locations indicated by the red rectangle in the left panel. The first spike after stimulus onset is marked in red. The average time-to-first-spike is indicated by the dotted red line, and serves as time point 0 in the right panel. Right: Relative spike latency for each recording location coded as a grayscale value. Adapted from Gollisch and Meister (2007).

Spatial Processing

Center-Surround Receptive Fields

Many ganglion cell types express antagonistic centersurround receptive fields, first described by Kuffler in 1953. The terms ON and OFF cells defined in the previous paragraph are a shorthand for ON center cell and OFF center cell, describing the response characteristics of the cells when they are stimulated in their receptive field

center. When a stimulus spot falls in the surround region, an ON center cell might respond when a bright spot is removed, that is, with an OFF-type response (point 2 below). In his 2001 work, Ralph Nelson summarized the effects that the surround can have on ganglion cell responses. Point 4 of the list given below is equivalent to a size tuning of the response, that is, responses to larger spots can be weaker than responses to smaller spots.

1.Change from sustained to transient center response as stimuli are displaced from center.

2.Responses evoked to opposite stimulus phase with surround stimulation.

3.Active inhibition of the center response with surround stimulation.

4.A maximal response can be evoked only with an optimally sized spot.

Center-surround receptive fields can be successfully modeled as difference of Gaussians, describing two overlaying concentric receptive fields with opposite effects on the cell (Figure 2). For small stimuli, the effect of the strong center receptive field prevails. For larger stimuli, the weaker surround begins to show its effect due to its larger radius. Physically, center responses originate from the excitatory input of bipolar cells to the ganglion cell dendrites. Usually, the size of the receptive field center of a ganglion matches the size of its dendritic field quite well. Surround properties originate from the activity of laterally oriented inhibitory interneurons in the retina, namely horizontal cells and amacrine cells. The activity of these cells contributes to the surround at three levels. They suppress the activities of bipolar cells either in the outer retina (horizontal cells) or inner retina (amacrine cells). Amacrine cells also give direct input to ganglion cells, contributing to the inhibitory surround at a third level of interaction.

Tiling

One of the properties characterizing a ganglion cell type is that its members tile the retina. This means that, as a population, the ganglion cells of any type carry information about the whole scene; a single ganglion cell is contributing one pixel. Ganglion cells with small receptive fields (e.g., midget ganglion cells) can convey spatial details of the visual scene (Figure 3(a), left column), while a ganglion cell with a large receptive field (e.g., parasol ganglion cells) will not be able to convey much detailed spatial information (Figure 1(a), right column) – the cell’s activity will signal that it was triggered from somewhere within its receptive field, but it is not possible to pinpoint the exact spatial location just from the activity of a single cell, or from the activity of the cell population. The situation is better when the ganglion cells of a type overlap (Figure 3(b)), a situation which is frequently