After photoinactivation, the phase pattern was radially homogeneous. Although the presence and implication of a radially varying phase profile

remain controversial (Nilsen and Russell, 1999, 2000; Rhode and Recio, 2000; Homer et al., 2004), this result provides further evidence that our technique diminished the cellular forces underlying the active process. Having established that photoinactivation of somatic motility dramatically reduces local amplification in the cochlea, we next used this tool to gauge the spatial extent of amplification and to observe how focal perturbation affects the accumulation of gain. We probed two narrow segments that extended roughly 50 μm along the cochlear partition: one region lying a full cycle basal to the traveling wave’s peak, and another situated just an eighth of a cycle before the peak. Inactivation of the more basal segment elicited a more gradual accumulation Apoptosis inhibitor of gain; this caused a small decrement in gain that persisted, but did not increase, up to the wave’s peak (Figure 4B). The modification did not significantly shift the wave’s peak, suggesting that the

inactivated segment lay near the beginning of the region of active amplification. This effect was confirmed in two additional experiments; SB431542 the average sensitivity at the wave’s peak remained 79% ± 12% of the control value. Perturbation in Carnitine palmitoyltransferase II a narrow segment near the active wave’s peak, in contrast, significantly reshaped the wave, indicating that local amplification is spatially nonuniform and increases near the peak (Figure 4C). In this instance, the traveling wave initially accumulated gain at a rate similar to that under control conditions. The cumulative gain ceased to grow in the inactivated region, over which some viscous loss was evident. Finally, gain began to accumulate again just beyond the

affected region. As before, the accumulation of local gain was abolished only in the segment of photoinactivation. This effect was confirmed in three additional experiments; the average sensitivity at the wave’s peak was reduced to 18% ± 4% of the control value. After washout of 4-azidosalicylate, there were occasionally slight offset changes in the overall sensitivity, but these were not consistent (Figures 4B and 4C). However, the elimination of local gain—the slope of the cumulative gain as a function of position—occurred consistently in the photoinactivated region. In addition, focal perturbation in narrow regions locally eliminated the radial phase lag at the outer hair cells (Figure S4). Impedance reconstructions based on these experiments indicate that inactivating the active process locally reduced negative damping and thus reveal the extent of the intrinsic positive damping by viscous forces (Figure 5).