Notably, the reduction at the orthogonal angle was larger than that at the preferred angle, making the absolute PSP tuning curve also appear sharper after integrating inhibition (Figure 3B, right). We summarized the inhibitory effect for all the simple cells. In our cell population, the selectivity of recorded PSP responses was similar to that of excitatory inputs (Figure 3C). Underlying

this apparent “linear” transformation are two concurrent nonlinear processes: the tuning selectivity existing in excitatory inputs would become significantly weakened or blurred when the inputs were transformed into PSP responses (Figure 3C; Vmsimu(E)); inhibitory inputs restored the level of PSP tuning back to that defined by the excitatory inputs (Figure 3C; Vmsimu(E+I)). The average tuning curves showed clearly that the PSP tuning was sharpened after integrating inhibition (Figure 3D). Screening Library in vitro Z-VAD-FMK molecular weight In addition, there was a larger reduction in PSP at the orthogonal angle than at the preferred angle (20.0 ± 4.3 versus 16.7 ± 4.1 mV, mean ± SD) (Figure 3E), indicating that inhibition had caused an additional sharpening of PSP

tuning beyond unselectively lowering responses at all orientations. Based on the derived PSP responses, we next estimated OS of spiking responses by applying a spike threshold in the integrate-and-fire neuron model (22 mV above the resting potential; see Experimental Procedures). Because PSP responses generated from excitatory inputs alone had a considerably flat tuning and most responses were above the spike threshold, OS would fail to be created in most of the cells (OSIAP < 0.3; Figure 3F; Simu(E)). In the presence of inhibition, however, derived spiking responses Carnitine dehydrogenase were as sharply tuned as those observed in loose-patch recordings (Figure 3F; Simu(E+I)). These data demonstrate that inhibition is indispensable for the generation of sharp OS in mouse simple cells. The above data have indicated that the intrinsic input-output transformation could lead to a blurring of tuning selectivity. To further illustrate this effect of membrane filtering, we carried out a more generalized simulation using the

neuron model. For simplicity, we simulated PSP responses resulting from model excitatory inputs that vary only in amplitude but not in temporal profile (see Experimental Procedures). The filtering property of the membrane is demonstrated in the plot of membrane potential depolarization versus excitatory conductance (Figure 4A, left). Within a physiological range of excitatory conductances (0.4 – 3.3 nS; see Figure 3C), the input-output function exhibited a fast saturating curve (Figure 4A, left, black). Its first-order derivative decreased rapidly to a small value (Figure 4A, left, inset), indicating that within a large input range the increase of the PSP response was much slower than the growth of the excitatory input strength.