, 1978; Schiller, 1992). Recently, however, there is growing evidence that, in the inner retina, crosstalk between the On and Off pathways generated via crossover circuits can change the receptive field properties of retinal

ganglion cells (Demb and Singer, 2012; Münch et al., 2009). To test whether crosstalk contributes to the reversal that we see, we blocked the On pathway using selleck screening library an mGluR6 agonist, L-AP4 (5–20 μM), that blocks input from photoreceptors to On bipolar cells (Slaughter and Miller, 1981). As expected, in the presence of L-AP4 (n = 24), all DSGCs showed no On response to stationary spots. The majority of these cells exhibited Off responses that were directionally tuned toward posterior directions (75%, 18/24 cells; Figure 5A), as previously described (Kittila and Massey, 1995). The remaining cells (25%, 6/24) were classified as non-DS. However, three of the non-DS cells displayed Off responses that were tuned to both posterior and anterior directions, making these cells axial selective rather than direction selective (Figure 5B; Figures S6A and S6B). In addition, four of the directionally tuned cells also presented a response toward

both directions, but the responses toward the ND were significantly smaller than the responses toward the PD. Interestingly, in these axial-selective cells, the timing of the response relative Selleck SB203580 to stimulation in the ND was different than the timing relative to stimulation in the PD (Figure S6C, Isotretinoin top). This implies that before adaptation, the delayed Off response to stimulation

in the original ND is masked by the On pathway. Hence, crosstalk between the On and Off pathways must normally contribute to the On-Off DSGC’s directional preference. Presenting the adaptation protocol to direction-selective and axial-selective cells (n = 21) in the presence of L-AP4 led to several changes in their responses to visual stimulation. First, a significant percentage of cells stopped responding to gratings (29%, 6/21), indicating that without On pathway signaling, a subset of cells loses its response to stimulation in the original PD and does not gain a new PD response. Second, cells that continued to respond to gratings showed reduced directional tuning (mean DSI decreased from 0.54 ± 0.23 to 0.18 ± 0.63), with 20% (3 out of 15) exhibiting a reversed PD (Figures 5A and 5B). Interestingly, the response timing relative to the stimulus resembled the timing relative to the stimulus when ND stimulation was given to axial-selective cells before adaptation (Figure S6C), indicating that the circuit mediating the ND response before adaptation in L-AP4 is identical to the circuit mediating the reversed response after adaptation. Third, after adaptation, 40% (6/15 cells) of the direction-selective and axial-selective cells exhibited an On response to a spot test (Figure 5A; Figures S6A and S6B).