Across-frequency nonlinear inhibition by GABA in processing of interaural time difference.

The barn owl uses the interaural time difference (ITD) to determine the azimuth of a sound source. Narrowband ITD-sensitive neurons cannot distinguish a given ITD from those that produce the same interaural phase difference (phase ambiguity). Neurons in the external nucleus of the inferior colliculus (ICx) resolve the ambiguity by gathering ITD information across many frequencies, thereby suppressing false responses (side peaks, SP) relative to the true ITD (the main peak, MP) in a response versus ITD curve. This process was quantitatively studied by comparing the ITD curve for a pair of tones presented simultaneously (two-tone curve) to the simple sum (predicted curve) of the individual ITD curves for the same tones presented separately. Sixteen of the 39 neurons tested did not show a significant difference in MP and SP responses between these curves (category I); 14 neurons showed significant SP suppression (category II). During iontophoretic application of bicuculline methiodide, a GABA(A) antagonist, most (n = 7/8) category II neurons lost nonlinear SP suppression and became linear, whereas category I neurons retained linear summation (n = 3/3). Thus, the nonlinear cross-frequency interaction of ITD responses in ICx neurons was mediated mostly by GABAergic inhibition, which enhanced SP suppression, and helped resolve phase ambiguity.