Based on these results, we chose the parameter values of the inhibitory-response function for subsequent simulations to be k = 10, S50 = 8, m = 5, and h = 15. The resulting switch-like CRP is shown in Figure 3C. Next, we tested whether this circuit model can produce adaptive shifts in the CRP switch value. We simulated two CRPs with RF stimulus strengths of 8°/s and 14°/s, respectively, and asked whether any combination of input and output divisive inhibition

(din and dout, respectively; (2) and (3)) could appropriately shift the CRP switch value. The ranges of din and dout tested, [0, 3] and [0, 0.24], respectively, were chosen such that the smallest value produced no modulation of the RF stimulus-response function, and the largest value produced 90% of the maximum possible modulation ( Figures S2A and S2B). All the parameters of the inhibitory-response function were maintained at the previous values, Linsitinib concentration chosen to yield Entinostat supplier switch-like CRPs. For each pair of din and dout values, we computed the switch values for the two CRPs and calculated them as the CRP shift ratio, the ratio of the shift in the switch value to the change in the RF stimulus speed; a ratio of 1 represents a perfectly adaptive shift. The plot of model CRP shift ratios as a function of din and dout demonstrated that

this circuit produced almost no shift in CRP switch values in response to an increase in the strength of the RF stimulus ( Figure 3D and Figure S2C). The maximum shift ratio produced was 0.03 (din = 1.5, dout = 0), and the two CRPs corresponding to this shift ratio are shown in Figure 3E. To understand why this circuit cannot produce adaptive shifts in the CRP switch value, we compared the patterns of inhibition in the two CRP measurement conditions. Because the activity of the inhibitory neuron (I) depended only on the strength of the competitor and not on the strength of the RF stimulus (I, sin and sout; Equation 4), the pattern of inhibition was identical in both cases ( Figure S2E; identical magenta and blue lines). Therefore, the

only difference between the two CRPs measured at the output unit was the upward (without a rightward) shift ( Figure 3E, blue curve relative to magenta Oxalosuccinic acid curve), reflecting the increased excitatory drive caused by the stronger RF stimulus (l in Equation 3). The simulations for Figure 3 explored a large portion, but not the entire space, of parameter values. Nonetheless, it is clear from the above observation that no possible combination of parameters for this circuit can produce adaptive, rightward shifts in the CRP when the strength of the RF stimulus is changed. Thus, feedforward lateral inhibition, as modeled with widely used divisive normalization (Equation 5), although able to produce switch-like CRPs, is unable to produce adaptive shifts in the CRP switch value.