, 2002). On the other hand, the results on cholinergic synaptic transmission between SACs and DSGCs contradicted the previous report that did not detect such a transmission (Fried et al., 2002). It is remarkable that the spatial symmetry of cholinergic and GABAergic synaptic connections between SACs and DSGCs were completely different, suggesting that synaptic connectivity between these two cell types is not based simply on the relative direction of the presynaptic

and postsynaptic selleck dendrites. Rather, the synaptic connectivity between SACs and DSGCs is controlled at a much more specific and local level, depending on the identity of the synapses as well as the direction of the dendrites. To demonstrate the presence of monosynaptic nicotinic and GABAergic transmissions from a SAC to a neighboring DSGC, we analyzed the synaptic delay of cholinergic and GABAergic transmissions under dual voltage clamp. The temporal delay between the onset of the presynaptic voltage pulse and the onset of postsynaptic current response was 6.61 ± 0.28 ms (mean ± SEM, n = 18) for cholinergic,

and 6.54 ± 0.30 (mean ± SEM, n = 18) for GABAergic transmission (Figures 2A and 2B). A large portion of this delay corresponded to the time required to activate presynaptic Ca2+ currents under our recording condition (data not shown) and was similar to some of the synaptic delays previously reported for other CNS synapses (Jo and Schlichter, 1999 and Jonas et al., 1998). However, the relative difference in synaptic delay between Z VAD FMK the cholinergic and GABAergic

responses was not statistically distinguishable (p = 0.48, not Figure 2C), suggesting that at least the initial GABAergic response was not mediated by polysynaptic transmission activated by cholinergic excitation. The presence of direct ACh-GABA cotransmission between SACs and DSGCs was further proven by uncaging Ca2+ from DM-nitrophen (loaded in SACs via the patch electrode) under the condition in which all potential Ca2+-dependent polysynaptic transmission was blocked by the Ca2+ channel blocker Cd2+ (300–500 μM). Ca2+ uncaging in a single SAC evoked rapid cholinergic and GABAergic responses from a neighboring DSGC (Figures 2D and 2E), demonstrating unequivocally ACh-GABA cotransmission between SACs and DSGCs in functionally mature rabbit retina. We next examined cholinergic and GABAergic contributions to the visual responses of DSGCs. A moving light bar elicited directionally asymmetric excitatory (EPSC) and inhibitory (IPSC) postsynaptic currents in DSGCs (Figure 3A). The IPSCs evoked by the null movement were much larger than those evoked by the preferred movement, as previously reported (Fried et al., 2002, Fried et al., 2005, Taylor and Vaney, 2002 and Weng et al.