The neuronal organization of the retina

Abstract

The mammalian retina consists of neurons of >60 distinct types, each playing a specific role in processing visual images. They are arranged in three main stages. The first decomposes the outputs of the rod and cone photoreceptors into ∼12 parallel information streams. The second connects these streams to specific types of retinal ganglion cells. The third combines bipolar and amacrine cell activity to create the diverse encodings of the visual world--roughly 20 of them--that the retina transmits to the brain. New transformations of the visual input continue to be found: at least half of the encodings sent to the brain (ganglion cell response selectivities) remain to be discovered. This diversity of the retina's outputs has yet to be incorporated into our understanding of higher visual function.

Figure 1. By the Standards of Other CNS Regions, Retinal Neurons Are Miniscule

(A) The layers of the mouse retina. A single bipolar cell is shown in white (adapted with permission from Wässle et al. (2009)). (B) The bipolar cell shown in A is reproduced at its correct scale on an image showing a cortical pyramidal cell. Cortical cell republished from (Gilbert, 1992).

Figure 2. The Types of Bipolar Cells Observed in the Mouse Retina

Note the different stratification within the inner plexiform layer and the molecular diversity of the cells. Reproduced with permission from Breuninger et al. (2011).

Figure 3. Divergence of the Cone Output into Separate Bipolar-Cell-Mediated Channels

(A) A single bipolar cell contacts all of the cones within its reach. (B) The dendritic arbors of the bipolar cells can overlap, and this means that each cone can be contacted by more than one bipolar cell. In this panel are shown two bipolar cells, each contacting all of the cones within their reach. Where the two bipolar cells partially overlap, they share a set of cones. For illustration, consider that these two cones transmit the same type of information away from the cones (both are shown in red). (C) The same two bipolar cells, contacting the same sets of cones, but this time transmitting different types of information away from the cones. (D) In fact, the dendritic arbors of ~12 types of bipolar cells overlap at any point on the retina. This means that the output of any particular cone is sampled by ~12 different bipolar cells. In principle, each of these types of bipolar cell carries a different reporting of the output of that cone. Four of the bipolar cells that contact one of the cone terminals (arrow) are shown here. Each of these can carry a different signal about the cone’s activity, as shown by the different colors in which they are drawn. (E) Left, structural diversity in three types of bipolar cell from the ground squirrel retina. The overlap of their dendrites shows that these three bipolar cells contact a nearly identical, overlapping, set of cones. Bipolar cells with axons that terminate in the upper half of the IPL are OFF type, whereas those that terminate in the bottom half are ON type. To the right are shown the responses of three morphological types of bipolar cells, two OFF and one ON, during light flashes of different durations. OFF bipolar cells hyperpolarize in the light and produce a transient depolarization at light OFF; ON bipolar cells display the opposite behavior. The shapes of the cb2 and cb3 cell light responses differ in subtle but characteristic ways. Previously unpublished bipolar cell images and responses are courtesy of Drs. Steven DeVries and Adam Light (see DeVries, 2000).

Figure 4. Bipolar Cells with Different Temporal Properties Give Rise to Ganglion Cells with Different Properties

For purposes of illustration, the spiking response of the ganglion cells is shown as though it were driven primarily by the bipolar cell, an approximation that ignores the contribution of amacrine cells. It is important to note that amacrine cells exert substantial control over the responses to light of the bipolar cells themselves. Amacrine cells have feedback synapses upon the axon terminals of the bipolar cells. The bipolar cells are small and electrotonically compact; as a consequence, the response recorded at the soma of a bipolar cell includes the effects of feedback by amacrine cells to that bipolar cell (see text). The stimulus to the bipolar cells was direct injection of current into a connected cone. The responses of bipolar cells are adapted from Saszik and DeVries (2012). Responses of the ganglion cells and bipolar cells are schematic; they do not derive from paired recordings.

Figure 5. The Structure and Generalized Connectivity of Narrow Field Amacrine Cells

(A) Type 7 glycinergic amacrine cell of the mouse retina. Note that this cell communicates “vertically,” interconnecting the ON and the OFF layers of the IPL. Cell image is adapted from Menger et al. (1998). (B) Block diagram of amacrine cell pathways. Amacrine cells receive input from bipolar cells and other amacrine cells. They make outputs back upon bipolar cells, to ganglion cells, or to other amacrine cells. Thus amacrine cells participate in feedback inhibition, feed-forward inhibition, and lateral inhibition. A single amacrine cell can have all of these arrangements or a subset of them.

Figure 6. Wide-Field Amacrine Cells Can Span Most of the Surface of the Retina

(A) Whole-mount view of a wide-field amacrine cell termed WA5-1 in the survey of Lin and Masland (2006). This cell’s axonal arbor (green) would affect visual stimuli falling in approximately half of the animal’s field of view. But the cell receives input from only a limited region of their dendritic fields (red), and presumably the population of cells of this type seamlessly affect images throughout the field, without the gaps that appear when a single cell or only a few of them are taken in isolation, as shown in (B). It does not take a large number of these cells to achieve the nearly complete axonal (green) coverage of the retina shown in (C). If we assume that the dendritic fields (ellipses) nearly tile the retina, the network of axonal processes is dense enough to affect the visual input with an adequate spatial resolution. In fact, the illustration shown here does not achieve tiling of the dendritic fields. If we assume a dendritic coverage of at least unity—higher than is shown here—the axonal coverage would blanket the retina at a very high density indeed. This is the arrangement to be predicted from other known types of retinal cells; whether or not it pertains to this cell will await a population stain. (D and E) These cells appear to mediate a variety of contextual effects, in which visual events surrounding a particular stimulus condition the response of a ganglion cell to that stimulus. An example is “object motion detection,” in which objects that move relative to the general visual field are preferentially reported to the brain (Ölveczky et al., 2003). The effect of this computation is artificially simulated in the lower panels. A native image is shown in (D). The image transmitted to the brain after object motion enhancement is shown in (E): the retinal ganglion cells respond most strongly to objects that are moving relative to the stationary surroundings. (D) and (E) reprinted from (Masland, 2003).

Figure 7. The Cardinal Features of the ON-OFF Direction-Selective Cell, and the Mechanism by Which Direction Selectivity Is Created

(A) The cell can discriminate the direction of motion of small stimuli falling within its receptive field (large circle), and it does not matter where within the field the small stimulus falls—there is a local subunit that is direction selective. (B and C) The fundamental mechanism of direction selectivity. (B) Shows the dendritic arbor of a starburst amacrine cell. A sector of the arbor (outlined in red) is (1) an independent functional unit, electrically separate from the rest of the cell, and (2) directionally polarized, such that it releases GABA when the stimulus moves in one direction—left to right in this example—and not in others. (C) Starburst sectors pointing in a single direction (red) selectively synapse upon dendrites of an ON-OFF DS ganglion cell (outlined by the black circle). In this example, they would provide inhibition when the stimulus moves from left to right. This cell would thus have a preferred direction for movement right-to-left and a null direction for movement left-to-right. The sectors are smaller than the dendritic field, thus accounting for the ganglion cell’s ability to discriminate small movements within the field. Other sectors of the starburst cell, pointing in other directions, would contact other direction selective ganglion cells; those cells would prefer different directions of stimulus movement.

Figure 8. How the Retina Surveys the World

Each type of retinal ganglion cell tiles the retinal surface, and thus covers every visual image completely. The tiles represented by different ganglion cell types are independent of each other. The different types of retinal ganglion cell sample the world through apertures of a different size (determined by the size of their dendritic field). Not only are their apertures different, the sensitivity to features of the stimulus within that aperture is different. This series of panels represents a visual image as sampled by four different types of ganglion cell of a generic subprimate mammalian retina, a subset from a total of about 20 ganglion cell types. (A) The traditional X/midget/brisk-sustained cell. This cell has a small receptive field center with an antagonistic surround, usually modeled as a difference of positive and negative Gaussians. This cell linearly sums inputs falling within its aperture. It therefore can effectively represent gradations of intensity. (B) The classic alpha/Y/brisk-sustained cell, which nonlinearly sums its inputs and is most sensitive to stimuli that change or move. Note that the sampling aperture (receptive field size) of this cell is large. It can report that something is moving, but cannot tell the brain where, within coarse bounds, the moving object is located. (C) Direction selective cells also have relatively large receptive fields. They transmit the information that something is moving within the receptive field, but, again, an individual cell cannot accurately tell the brain where inside the receptive field the stimulus lies. (D) Color coded cells. These report where on the axis from blue to green the spectrum of light within the cell’s receptive field is located. In a generic mammalian retina, which has only one short wavelength and one long wavelength cone, this information is transmitted by the blue-ON and blue-OFF ganglion cells.