Visual Signal Processing in the Inner Retina

Fig. 1. A cross-sectional view of retinal layers and the main vertical and lateral signaling pathways. The retina is organized into three cellular layers, rod (R) and cone (C) photoreceptor somas are located in the outer nuclear layer (ONL); horizontal cell (HC), bipolar cell (BC), and amacrine cell (AC) somas are located in the inner nuclear layer (INL); ganglion cell (GC) somas are located in the ganglion cell layer (GCL). Synaptic connections between photoreceptors, bipolar cells, and horizontal cells are made in the outer plexiform layer (OPL). Synaptic connections between bipolar cells, amacrine cells, and ganglion cells are made in the inner plexiform layer (IPL). Vertical signaling pathways are composed of photoreceptors, bipolar cells, and ganglion cells. Two lateral pathways, comprised of horizontal cells in the OPL and amacrine cells in the IPL, modulate the flow of information along the vertical pathway.

VISUAL INFORMATION IS FIRST PROCESSED IN THE OPL

Photoreceptors transduce light into electrical signals, which are processed by retinal interneurons before being sent to the brain. In the first synaptic layer, horizontal cells make synaptic contacts with photoreceptor terminals (Fig. 1). One outcome of this interaction is the establishment of an antagonistic center/surround receptive field organization, which can be revealed by stimulating the retina with light spots of different sizes. Illumination of the receptive field center with a small spot of light alters the activity of photoreceptors, which integrate inputs over small areas. Illumination of the larger receptive field surround alters the activity of horizontal cells, which feed back to the photoreceptor, antagonizing the effects of center illumination [1]. The antagonistic center/surround organization of receptive field is a fundamental feature of bipolar and ganglion cells [2, 3]. In the retina, this receptive field organization contributes to contrast perception, edge detection, and color processing [4, 5]. Additional center-surround signal processing also occurs in the IPL, as described next.

BIPOLAR CELLS FORM PARALLEL PATHWAYS AND PROVIDE EXCITATORY INPUT TO THE IPL

At the OPL, the processed photoreceptor output is relayed to the IPL by a variety of bipolar cell types that form parallel signaling pathways (reviewed in [6, 7]). Excitatory inputs to the IPL originate from the two main functional classes, ON and OFF bipolar cells. ON bipolar cells depolarize in response to increasing illumination within their receptive field centers, and OFF bipolar cells depolarize in response to decreasing illumination within their receptive field centers. The distinct responses of

Fig. 2. Bipolar cells form parallel retinal signaling pathways. Vertical view drawings of neurobiotin stained bipolar cells from rat retina illustrate distinct morphological subtypes. A similar diversity of bipolar cells exists in retinas of other mammalian and cold-blooded vertebrates. The axon terminals stratify at different depths of the inner plexiform layer (IPL). ON bipolar cells have axons that terminate in the inner half of the IPL (ON sublamina), and OFF bipolar cells have axons that terminate in the outer half of the IPL (OFF sublamina). Rod bipolar cell (RB) dendrites exclusively contact rods. The remaining cone bipolar cells (CB) only contact cones. GCL ganglion cell layer, INL inner nuclear layer, OPL outer plexiform layer (Used with permission of the American Physiological Society, from [47].)

ON and OFF bipolar cells are determined by separate classes of glutamate receptors present on their dendrites. Glutamate is continuously released by photoreceptors in the dark and depolarizes OFF bipolar cells by activating α-amino-3-hydroxy-5-methyl-4- isoxazol-propionic acid (AMPA) and kainate types of ionotropic glutamate receptors on their dendritic processes [8, 9]. ON bipolar cells, by contrast, are hyperpolarized by glutamate that activates dendritic metabotropic mGluR6 (metabotropic glutamate receptor 6) receptors [10, 11]. In the light, when glutamate release is decreased, ON bipolar cells depolarize, and OFF bipolar cells hyperpolarize.

These broad ON and OFF bipolar cell classes are divided further into several subtypes of ON and OFF bipolar cells (reviewed in [6]). In mammalian retina, at least nine morphological classes of ON and OFF bipolar cells receive input from cones, and one class receives input exclusively from rods (Fig. 2). A similar variety of ON and OFF bipolar cells exists in salamander; however, these bipolar cells receive mixed inputs and are either cone or rod dominant [12]. The morphological subtypes of ON and OFF bipolar cells have unique functions. In mammals, ON rod bipolar cells contact rods exclusively and transmit rod signals to the IPL. The remaining bipolar cell types relay different cone signals to the IPL. Some types of cone bipolar cells relay color information between cones and ganglion cells. For instance, midget bipolar cells comprise the red-green signaling pathway and transmit red and green spectral information. The blue cone bipolar cells receive input exclusively from blue cones and comprise the blue pathway. Another cone bipolar cell class, called diffuse bipolar cells, transmits luminosity information without encoding spectral information (“color blind”).

The electrical responses of separate bipolar cell classes to photoreceptor input are distinct, consistent with the notion that bipolar cells separate the visual input into parallel signals. How is the photoreceptor input separated into different signals? Distinct gluta-