We scaled the excitatory synaptic amplitude by a factor of 0.8–1.2, while keeping the inhibitory response amplitude unchanged (see Figure 4E). Figure 5F shows the frequency tuning curves of peak Vm responses at different excitatory scaling factors. To derive spiking response HIF-1�� pathway from the peak Vm response, we utilized a power-law function in describing the relation between Vm and spike rate (Atallah et al., 2012, Liu et al., 2011, Miller and Troyer, 2002 and Priebe, 2008) (see Experimental Procedures). As shown in Figure 5G, the

scaling of excitatory response amplitudes resulted in negligible changes in the shape of spike tuning, although the spike rate could be modulated by as much as 50%. Within the experimentally observed range of changes of spike rate (0.4- to 1.4-fold, see Figure 1D), excitation was scaled within a range of 0.78- to 1.12-fold, and spike tuning width only varied between a narrow range of 0.93- to 1.03-fold (Figure 5H). Similar, as previously reported (Atallah et al., 2012), scaling of inhibition can also achieve an approximate gain control of spike responses (Figure 5I). The gain modulation by scaling excitation was not affected much by the inhibitory tuning shape, as similar effects on spike tuning were achieved under inhibition cotuned with excitation, more broadly tuned than excitation, or inhibition with

a flat tuning (Figure 5J). Previous studies have demonstrated that the amplitude of binaural spike response

can be modulated by interaural Pomalidomide in vitro level/intensity difference (ILD), a spatial location cue (Irvine and Gago, 1990, Kuwada et al., 1997, Li et al., 2010, Pollak, 2012, Semple and Kitzes, 1985 and Wenstrup et al., 1988). In the experiments described thus far, ILD was set as zero to simulate a sound source originating on the auditory midline. To test whether a linear transformation of the contralateral into binaural spike response also applies to other binaural hearing conditions, we varied ILD to simulate different TCL sound source locations. As shown by an example cell in Figure 6A, the binaural TRFs at several different ILDs all resembled the TRF under contralateral stimulation alone. At each ILD tested, a strong linear correlation between binaural and contralateral spike responses was observed (Figures 6B and 6C). Noticeably, the gain value decreased as ILD became increasingly ipsilaterally dominant, suggesting the progressively increasing influence of ipsilaterally mediated suppression at more ipsilaterally dominant ILDs (Figure 6C). In a total of 24 similarly recorded neurons, except for two cells exhibiting enhancement, the majority of cells showed a reduction of binaural spike response with decreasing ILD (Figure 6C). The linear correlation between binaural and contralateral spike responses was similarly strong (r close to 1) at all testing ILDs and in all the cells examined ( Figure 6E), indicating that gain modulation is a general phenomenon.