Along these lines, previous studies have shown APB has a much greater effect on reducing spontaneous activity among On-center RGCs compared to Off-center RGCs (Knapp and Mistler, 1983 and Horton and Sherk, 1984). Given the unexpected finding that intraocular APB can induce a switch in the response signature of On-center LGN neurons, we wished to

confirm that the LGN, rather than the retina, is the site of this rapid plasticity. We therefore stimulated the retina with the same visual stimulus shown in Figure 1 and recorded electroretinograms (ERGs) in vivo (n = 4) and single-unit responses from On-center RGCs in vitro (n = 32) before and during APB application. As shown in Figure 2, see more APB silenced On responses in the retina without any indication of emergent Off responses. More importantly, every On-center cell became visually unresponsive with APB, indicating APB and our injection protocol blocked visual responses in On center RGCs and the On to Off plasticity measured in the LGN did not simply follow a similar transition in the eye. Having observed a striking

APB-induced flip in the response signature of On-center LGN neurons using a spatially-uniform stimulus, we next examined the effects of APB on the fine structure of LGN receptive fields by using a white-noise stimulus and reverse-correlation analysis (Figure 3; see Experimental Procedures). As expected and exemplified with the receptive field map of a representative Off-center neuron in Figure 3A, all Off-center neurons in our sample remained Off-center in the presence of APB (n = Talazoparib clinical trial 28 cells). In contrast, >50% of On-center neurons (n = 35/52) underwent PDK4 the rapid transformation in receptive field structure from On-center to Off-center, as in Figures 3C–3E. The remaining On-center neurons were nonresponsive to visual stimuli following APB treatment (n = 17). Using receptive field size and response

latency to classify cells as either X or Y (Usrey et al., 1999), we did not see a significant difference in the relative proportion of X and Y cells in the group of On-center cells that lost visual responsiveness following APB application versus those that developed Off-center responses (p = 0.9, Wilcoxon rank sum test). We next compared the size and location of the emergent Off-center receptive fields to the original On-center receptive fields. To do so, we fit the original and emergent receptive field centers to a Gaussian equation and normalized coordinate distances by the size of each neuron’s original receptive field center (in space constants, see Experimental Procedures). Because intraocular injections can alter eye position and therefore the location of receptive fields, this analysis was only performed on cells simultaneously recorded with an Off cell whose receptive field served as a fiduciary marker (n = 13 cells).