distinct inputs, the release time course sensed by GABAC receptors may be distorted by the saturation and slow deactivation of these receptors, obscuring a common input. Inspection of the apparent GABAC receptor release function reveals a prolonged tail, not observed with GABAA receptors, which is consistent with the spillover activation of GABAC receptors.

Because GABAC receptors are more sensitive to GABA than GABAA receptors, they may be activated by low concentrations of GABA that spill over from neighboring release sites. When GABA spillover is enhanced, by either reducing uptake or enhancing release, the GABAC, but not the GABAA, receptor-mediated component of light-evoked inhibition is selectively increased [52]. GABA spillover leads to stronger GABACR-mediated presynaptic inhibition, larger reductions in glutamate release, and reduced ganglion cell excitation [52]. Taken together, these data suggest that, in addition to slow receptor kinetics of GABACRs, spillover contributes to the prolonged GABACR- mediated responses.

Glycine, the Other Inhibitory Transmitter

About one half of all amacrine cells are glycinergic, and there are eight types of glycinergic amacrine cells [53]. Anatomical evidence suggests that rod and OFF cone bipolar cells receive input from glycinergic amacrine cells [54, 55]. Physiological recordings of spontaneous [56] and light-evoked [74] glycinergic inhibitory currents have shown that presynaptic inhibition was most prominent in OFF cone bipolar cells and was also observed in rod bipolar cells, but not in ON cone bipolar cells.

Slow rod signals are transmitted from rod bipolar cells to OFF bipolar cell terminals by AII (or rod) amacrine cells. This light-evoked presynaptic inhibition is slow, matches the time course of rod signaling, and is mediated by glycine [74]. There is an apparent mismatch between the slow L-IPSC time course and fast kinetics of the glycine receptors [56]. This discrepancy can be reconciled when one considers that the time course of glycine release from AII amacrine cells is likely to be sustained, similar to its sustained light-evoked depolarization [57, 58]. Thus, the time course of glycinergic inhibition is matched to the slow rod signal time course, but the time course is determined by transmitter release and not receptor properties.

Lateral Versus Vertical Inhibitory Pathways in the IPL:

The Story of Two Inhibitory Neurotransmitters

Why does the IPL utilize two inhibitory transmitters, GABA and glycine? Although both of these transmitters gate chloride channels, these two transmitters are utilized by distinct signaling pathways. In mammalian retina, GABAergic amacrine cells have wide-field processes and are confined to the same laminae and signal laterally [6]. By contrast, the processes of glycinergic amacrine cells have narrow extents, but are typically multistratified and signal vertically between different laminae [6, 53].

GABAergic lateral inhibition plays a critical role in the processing of spatial information. Wide-field GABAergic amacrine cells contribute to the receptive field surround of ganglion cells [44, 45]. Cook and McReynolds [44] suggested that amacrine cell surround input mediates a finer spatial filtering that occurs after the coarser spatial filtering in the OPL, attributed to horizontal cell surround signaling. Wide-field GABAergic amacrine

cells synapse onto bipolar cell terminals and ganglion cell dendrites. Thus, there are two IPL surround signaling pathways: direct GABAergic inhibition of ganglion cells [44] and presynaptic GABAergic inhibition that limits bipolar cell signaling to ganglion cells [45, 46]. It remains to be seen whether similar or different classes of amacrine cells mediate preand postsynaptic wide-field inhibition.

Glycinergic amacrine cells have narrow-field processes that extend vertically across the IPL and mediate signaling between different sublamina [14, 43]. The best-described glycinergic amacrine cell is the AII or rod amacrine cell. Rod bipolar cells do not directly contact ganglion cells. Instead, they signal through an AII amacrine cell intermediate that contacts ON and OFF cone bipolar cells, which in turn signal ganglion cells. The AII amacrine splits the ON rod bipolar cell input into an inhibitory glycinergic output to OFF cone bipolar cell terminals [59] and excitatory, electrical output to ON cone bipolar cell terminals, mediated by gap junctional connections [60]. In contrast to wide-field GABAergic amacrine cells that signal laterally within IPL strata, narrow-field glycinergic cells signal vertically between IPL strata.

Parallel Ganglion Cell Output Pathways

Parallel bipolar cell-signaling pathways relay different aspects of the visual signal to 10–15 morphological types of ganglion cells [6, 61]. As noted, amacrine cells modulate the information transferred between bipolar and ganglion cells. This information is then sent by distinct ganglion cells that comprise parallel signal pathways to different parts of the brain. Like bipolar cells, ganglion cells are divided into two major ON and OFF classes, which convey information about light increments and decrements in their receptive field’s center, respectively, and both classes possess antagonistic surrounds [2]. ON and OFF types can be further divided into X and Y cells that summate inputs linearly and nonlinearly, respectively [62]. They respond to illumination in either a sustained (X) or transient (Y) fashion, similar to bipolar cells. In cat retina, these Y and X ganglion cell classes form distinct morphological types, α- and β-ganglion cells, respectively [63]. Transient bipolar cell terminals and Y ganglion cell dendrites costratify in the middle IPL strata, while sustained bipolar cell terminals and X ganglion cell dendrites costratify at the innerand outermost strata of the IPL. The X and Y ganglion cells are similar to the parvo (P) and magno (M) classes of primate ganglion cells, which correspond to the morphological midget and parasol classes, respectively (reviewed in [64]). Parvo ganglion cells transmit visual information about form and color (what is it?), while magno ganglion cells transmit information about motion and spatial relationship (where is it?) to the lateral geniculate nucleus (reviewed in [65]).

Ganglion Cells Encode Color Information

Midget ganglion cells encode color information and relay it to the brain. Like the midget bipolar cells, midget ganglion cells comprise the red-green pathway. This redgreen color opponent pathway is most pronounced in the central retina and is attributed to the unique circuitry of the midget system. Their center response is determined by a strong single red or green cone input, while the surround is determined by weak mixed cone inputs, resulting in color opponency. A unique bistratified ganglion cell that is excited by blue light, via blue bipolar cells, makes contacts at the inner IPL, and that