Precise inhibition is essential for microsecond interaural time difference coding

Microsecond differences in the arrival time of a sound at the two ears (interaural time differences, ITDs) are the main cue for localizing low-frequency sounds in space. Traditionally, ITDs are thought to be encoded by an array of coincidence- detector neurons, receiving excitatory inputs from the two ears via axons of variable length ('delay lines'), to create a topographic map of azimuthal auditory space(1,2). Compelling evidence for the existence of such a map in the mammalian ITD detector, the medial superior olive (MSO), however, is lacking. Equally puzzling is the role of a-temporally very precise(3)- glycine-mediated inhibitory input to MSO neurons. Using in vivo recordings from the MSO of the Mongolian gerbil, we found the responses of ITD-sensitive neurons to be inconsistent with the idea of a topographic map of auditory space. Moreover, local application of glycine and its antagonist strychnine by iontophoresis (through glass pipette electrodes, by means of an electric current) revealed that precisely timed glycine- controlled inhibition is a critical part of the mechanism by which the physiologically relevant range of ITDs is encoded in the MSO. A computer model, simulating the response of a coincidence-detector neuron with bilateral excitatory inputs and a temporally precise contralateral inhibitory input, supports this conclusion