Modeling suggests that even a small dendritic voltage gradient in combination with voltage-gated channels could generate a robust DS signal in SAC dendrites (Hausselt et al., 2007). In another model it was proposed, that SACs generate a Cl− concentration gradient along their dendrites due to a differential distribution of Cl− intruders and extruders, and that this results in GABAergic input causing depolarization at the proximal and hyperpolarization selleckchem at the distal dendrite, respectively (for details see Enciso et al., 2010, Gavrikov et al., 2003 and Gavrikov et al., 2006). According to this model, the asymmetry in the effect

of GABAergic inputs leads to dendritic direction selectivity. Other than the voltage gradient model, the Cl− gradient model requires GABAergic input and therefore does not account for the finding that SAC responses remain DS in the presence of GABA receptor blockers (see below). Ultrastructural (Millar and Morgan, 1987) and

functional data (Zheng et al., Dasatinib in vivo 2004) indicate that mature SACs form reciprocal GABAergic synapses, which have been implicated in the computation of DS signals (e.g., Münch and Werblin, 2006). If a SAC is excited, it inhibits its neighbor—this in turn reduces the neighbor’s GABA release and in effect enhances the first SAC’s response. Such interaction may sharpen the DS contrast in neighboring SAC dendrites pointing in opposite directions (Lee et al., 2010 and Lee and Zhou, 2006). However, since GABA receptor antagonists do not abolish dendritic direction selectivity in SACs (Euler et al.,

2002, Hausselt et al., 2007 and Oesch and Taylor, 2010), it is unlikely that these interactions are essential for the SAC’s intrinsic DS mechanism. In addition to inhibition, DS ganglion cells receive DS excitatory input from bipolar cells (Fried et al., 2005). This tuning could arise from DS suppression of bipolar cell output by GABAergic amacrine cells (Figure 5E), which would explain why this excitatory DS pathway is eliminated by ADP ribosylation factor GABA receptor blockers (see The Role of Inhibition). Because ablating SACs abolishes ganglion cell DS responses (Amthor et al., 2002 and Yoshida et al., 2001), it is likely that SACs are involved in tuning bipolar cell output—if other amacrine cells were crucial, some residual direction selectivity after ablation would be expected. Besides glutamatergic excitation, DS ganglion cells also receive excitatory cholinergic input from SACs (reviewed in Vaney et al., 2001). Blocking cholinergic receptors in the presence of GABA receptor antagonists reduces the responses of DS ganglion cells independent of motion direction (Chiao and Masland, 2002), suggesting that cholinergic excitation provides motion-sensitive but not DS excitation (He and Masland, 1997). On the other hand, there is also evidence that this cholinergic input is DS (Figure 5C, Fried et al., 2005 and Lee et al., 2010).