This manifests Angiogenesis inhibitor in a more nonlinear contrast response function ( Figure 2B) with greater sensitivity for higher contrasts. The decrease in the Ca2+

channel maximum conductance also explains the lower gain seen at maximum luminance ( Figure 1D). This highlights the presynaptic terminal of bipolar cells as a key site for regulating the transmission of visual signals through the retina. As well as the dramatic gain reduction, the OFF pathway also becomes more sensitive to dimmer light. As the expected effects of reduced dopamine will shift the Cav activation to more depolarized potentials, it is unlikely to explain the increased luminance sensitivity. However, D1 receptors do enhance glutamate-gated ionic channels in OFF bipolar cells click here (Maguire and Werblin, 1994). When D1 receptors are activated, ionotropic glutamate receptors generate enhanced current that will result in OFF bipolar cells being less sensitive to small decreases in glutamate concentration; a similar phenomenon has been described in horizontal cells (Knapp and Dowling, 1987). The olfacto-retinal circuit endows the vertebrate visual system with the ability to quickly reduce the gain and increase the sensitivity of the retina in the presence of food, independently of changes in mean luminance. A behavior

that is likely to be related to this process has recently been described by Stephenson et al. (2011), who found that zebrafish show a preference for darker areas in their environment when background levels of light are low, and brighter areas when background light levels are high. An olfactory stimulus applied in low background would then mimick the effects of light adaptation by encouraging fish to explore brighter areas. The reduction in gain of bipolar cell synapses transmitting the visual signal to the inner retina (Figure 1), as well as the increase in sensitivity to high contrast (Figure 2), is likely all to be one of the mechanisms by which an olfactory stimulus allows the visual system of the zebrafish to operate in brighter areas. In the future, it will

be interesting to investigate the behavioral consequences of a selective decrease in gain of the OFF pathway. Certainly it would be expected to help the retina avoid saturation under bright conditions, but then so would a decrease in gain through the ON pathway. A possible explanation for the selective control of the OFF pathway might lie in the recent study of Ratliff et al. (2010) who asked why OFF RGCs are so much more numerous than ONs in most retinas (including zebrafish). They found that natural scenes contain an excess of negative spatial contrasts over positive, leading to the suggestion that the excess of OFF RGCs is a structural adaptation of the retina to the excess of darkness in natural scenes. In zebrafish, OFF bipolar cells outnumber ONs by a ratio of 3:1 (Odermatt et al.