Interaural Time Difference Processing in the Mammalian Medial Superior Olive: The Role of Glycinergic Inhibition

Abstract

The dominant cue for localization of low-frequency sounds are microsecond differences in the time-of-arrival of sounds at the two ears [interaural time difference (ITD)]. In mammals, ITD sensitivity is established in the medial superior olive (MSO) by coincidence detection of excitatory inputs from both ears. Hence the relative delay of the binaural inputs is crucial for adjusting ITD sensitivity in MSO cells. How these delays are constructed is, however, still unknown. Specifically, the question of whether inhibitory inputs are involved in timing the net excitation in MSO cells, and if so how, is controversial. These inhibitory inputs derive from the nuclei of the trapezoid body, which have physiological and structural specializations for high-fidelity temporal transmission, raising the possibility that well timed inhibition is involved in tuning ITD sensitivity. Here, we present physiological and pharmacological data from in vivo extracellular MSO recordings in anesthetized gerbils. Reversible blockade of synaptic inhibition by iontophoretic application of the glycine antagonist strychnine increased firing rates and significantly shifted ITD sensitivity of MSO neurons. This indicates that glycinergic inhibition plays a major role in tuning the delays of binaural excitation. We also tonically applied glycine, which lowered firing rates but also shifted ITD sensitivity in a way analogous to strychnine. Hence tonic glycine application experimentally decoupled the effect of inhibition from the timing of its inputs. We conclude that, for proper ITD processing, not only is inhibition necessary, but it must also be precisely timed.

Medial Superior Olivary Neurons Receive Surprisingly Few Excitatory and Inhibitory Inputs with Balanced Strength and Short-Term Dynamics

“…In the mammalian MSO, inhibition is crucial for the proper tuning of ITD sensitivity (Brand et al, 2002;Pecka et al, 2008) and it has been suggested that precisely timed inhibitory drive sets the time window for neuronal coincidence detection (Pecka et al, 2008). Thus, if STD supports coincidence detection, and if the inhibitory inputs to the MSO are temporally aligned to the excitation, both the excitation and inhibition should have similar STP profiles.…”

“…In vivo studies show that MSO neurons can fire at very high rates, locking precisely to the phase of pure tones (Brand et al, 2002). Thus, given this circuit relies on temporally precise inhibition and excitation (Brand et al, 2002;Pecka et al, 2008), we expect these inputs to behave similarly during high-frequency stimulation in vitro. Therefore, we hypothesize that the recruitment of a set of strong and fast synaptic inputs establishes the presynaptic basis for the exquisite coincidence detection in MSO neurons.…”

“…Additionally, the lateral nucleus of the trapezoid body (LNTB) contributes a minor inhibitory input to this circuit. The temporal alignment of these inputs are vital to maintaining physiologically relevant ITD coding (Brand et al, 2002;Pecka et al, 2008).…”

Modeling Binaural Responses in the Auditory Brainstem to Electric Stimulation of the Auditory Nerve

“…We focused on the sustained response because responses of IC neurons to electric pulse trains are often limited to brief burst of spikes at stimulus onset at high stimulation rates (Smith and Delgutte 2007;Hancock et al 2012). These electric responses contrast with responses to acoustic pure tones which show sustained response throughout stimulus durations in a majority of IC and MSO neurons (Pecka et al 2008).…”

A Model of the Medial Superior Olive Explains Spatiotemporal Features of Local Field Potentials

“…Juxtacellular and intracellular whole-cell in vivo data have only recently been reported (Franken et al, 2013;van der Heijden et al, 2013). In the absence of a large corpus of intracellular or even extracellular data, debates continue regarding the distribution of interaural delays (McAlpine and Grothe, 2003;Joris and Yin, 2007) and the kinetics and timing of inhibition (Brand et al, 2002;Grothe, 2003;Zhou et al, 2005;Pecka et al, 2008; and excitation (Jercog et al, 2010;. Systematic theory-based analyses of the neurophonic, a more accessible in vivo data source, may offer new perspectives on these puzzles and provide a bridge between in vivo data obtained in larger species (cat, dog, monkey) and small-headed rodents (gerbil, guinea pig, chinchilla).…”