Elsevier

Hearing Research

Volume 279, Issues 1–2, September 2011, Pages 43-50
Hearing Research

Dynamics of binaural processing in the mammalian sound localization pathway – The role of GABAB receptors

https://doi.org/10.1016/j.heares.2011.03.013Get rights and content

Abstract

The initial binaural processing in the superior olive represents the fastest computation known in the entire mammalian brain. Although the binaural system has to perform under very different and often highly dynamic acoustic conditions, the integration of binaural information in the superior olivary complex (SOC) has not been considered to be adaptive or dynamic itself. Recent evidence, however, shows that the initial processing of interaural level and interaural time differences relies on well-adjusted interactions of both the excitatory and the inhibitory projections, respectively. Under static conditions, these inputs seem to be tightly balanced, but may also require dynamic adjustment for proper function when the acoustic environment changes. GABAB receptors are at least one mechanism rendering the system more dynamic than considered so far. A comprehensive description of how binaural processing in the SOC is dynamically regulated by GABAB receptors in adults and in early development is important for understanding how spatial auditory processing changes with acoustic context.

Highlights

► Initial binaural processing in the mammalian auditory brainstem is dynamic. ► Synaptic strength in olivary nuclei is controlled via pre-synaptic GABAB receptors. ► GABAB mediated suppression controls the balance of excitation and inhibition. ► Lateral superior olivary neurons control their inputs via dendritic release of GABA. ► The source of GABA in the medial superior olive is still unclear.

Introduction

The auditory system performs an extraordinary task: it has to “construct” the entire auditory world that we experience from the movement of the two eardrums. This challenge becomes particularly obvious if we consider the processing of auditory space in our brain. There is no spatial information mapped onto the auditory receptor surface, the cochlea. Therefore auditory space has to be constructed by central computations, which are based on the analysis of (1.) the spectral characteristics related to the vertical position of a sound (as well as to rear-to-front differences) and (2.) differences in sound level and time-of-arrival of a sound at the two ears. The binaural disparities in sound level (interaural level differences; ILD) and time (interaural time differences; ITD) are minute and require neuronal computation with exquisite resolution (e.g. the temporal resolution of a few microseconds ITD and around 1 dB ILD; recently reviewed in Grothe et al., 2010). This degree of precision has led us to more or less neglect the possibility that this system is not only very precise but also surprisingly dynamic. Only very few studies dealt with its capacity to dynamically adapt to stimulus history or binaural context (Finlayson and Adam, 1997, Park et al., 2008, Dahmen et al., 2010), although the changes of binaural cues occurring in natural and, in particular, in human-made environments are quite drastic (Blauert, 1996, Meffin and Grothe, 2009). Moreover, only very recently mechanisms were revealed that may help the system to adjust to the large variation of acoustic environments and their dynamics.

In mammals, the focus of this review, binaural sound localization mechanisms are based on fast and exquisitely balanced interactions of synaptic inputs from both ears (reviewed in Grothe et al., 2010). [It should be noted, that binaural processing is essential not only for computing the location of sound sources in the horizontal plane, but also for sound segregation, a prerequisite for being able of “tuning in” to a single speaker for instance at a cocktail-party]. This is most obvious in ILD coding in the lateral superior olive (LSO) which is based on neuronal subtraction of a contralateral inhibition from an ipsilaterally driven excitation (see below). There is also increasing evidence of an essential contribution of inhibitory inputs in coincidence detection in the ITD processing structure, the medial superior olive (MSO). Recent studies show that the interactions of the different excitatory and inhibitory inputs to LSO and MSO are surprisingly dynamic (Finlayson and Adam, 1997, Hermann et al., 2007, Magnusson et al., 2008, Park et al., 2008, Hassfurth et al., 2010, Couchman et al., 2010). This is at least partially due to dynamic changes of synaptic input strength controlled by GABAB receptor activation in these nuclei. GABAB receptors are abundant in the entire brain. Activation of these receptors either opens K+-channels thereby hyperpolarizing the postsynaptic neuron, or inhibits pre-synaptic Ca++-channels, both resulting in a decreases of transmitter release (Kornau, 2006, Ulrich and Bettler, 2007). In the LSO (Magnusson et al., 2008) and the MSO (Hassfurth et al., 2010) GABAB receptor activation differentially modulates the excitatory versus inhibitory inputs.

This is relevant for our understanding of the basis of sound localization and sound segregation and how the system can adapt to changes in acoustic context or sudden changes in sound pressure. Moreover, there is increasing evidence for considerable age-related changes in the inhibitory systems indicating a significant role of synaptic balancing in age-related hearing deficits (Caspary et al., 2008).

Section snippets

ILD processing in the lateral superior olive

ILD is the main cue for horizontal localization of high frequency sounds. The definition of “high-frequency” is simply frequencies with wave lengths shorter than the inter-ear-distance. Only for these sounds the shadowing effect of the head creates significant attenuation (resolution of humans around 1–2 dB ILD) for sounds in the far-field. For near-field sound sources (approximately within arm-length) ILDs are also created for lower frequencies.

ILDs are initially processed in the LSO, which

Modulation of inhibitory and excitatory synaptic efficacy by GABAB receptors in the auditory brainstem

To our knowledge, David Larue and Jeffrey Winer (unpublished data presented at an SfN Poster in 2001) were the first to indicate prominent GABAB receptor staining in the auditory brainstem of the cat, including the LSO and MSO. In the gerbil auditory system we have found similar staining patterns with prominent staining against the GABAB receptors in all nuclei of the superior olivary complex especially in the LSO (Fig.2A) and the MSO (Fig.2B). It is generally known that GABAB receptors, which

The origin of GABA release in the adult superior olivary complex

In the previous section we described the effects of pharmacological GABAB receptor activation with the synthetic GABAB receptor agonist Baclofen on synaptic transmission in the auditory brainstem. Yet, the endogenous GABAB receptor activator is GABA, which is generally released from pre-synaptic terminals that are opposite to postsynaptic GABAA receptor aggregations. This poses a potential dilemma in the mature LSO and MSO, since the main inhibitory projections from the MNTB become purely

The role of GABAB receptors in the SOC prior to hearing onset

Before hearing onset, GABAB receptor antibody staining is abundant in the MSO (Heise et al., 2005, Hassfurth et al., 2010) and LSO (unpublished observation). If GABAB receptors in the hearing animal dynamically adjust the relative balance of excitation and inhibition and thereby fine-tune ILD and ITD coding, what is then their role prior to hearing onset?

This question has been primarily investigated in the MSO. Before hearing onset pharmacological activation of GABAB receptors has a strong

GABAB receptor distribution and function in the avian auditory brainstem

In contrast to the mammalian bushy cells and MSO neurons, the avian analoga Nucleus magnocellularis (NM) and Nucleus laminaris (NL), receive a major GABAergic input from the superior olivary Nucleus (SON), which remains GABAergic also in adult animals (Burger et al., 2005a). This GABAergic inhibition controls frequency tuning in NM (Fukui et al., 2010) and sharpens coincidence detection in NL (Funabiki et al., 1998, Monsivais et al., 2000, Nishino et al., 2008). GABAB receptor expression is

Functional implications of GABAB receptor activation for sound localization in mammals

We will now turn to the most important question: What is the functional significance of GABAB receptor activation for sound localization?

We are only beginning to understand this issue in the ILD processing circuit in the LSO. A functional analysis of the effect of GABAB receptors on ILD coding was performed in LSO neurons by measuring the spike response of these neurons to binaural sounds at various ILDs under control conditions and during pharmacological GABAB receptor blockade or activation (

Conclusions and outlook

As outlined in this article, binaural processing in the superior olivary complex is not static but specifically modulated by GABAB receptor activation. In these nuclei, GABAB receptor activation does not have a generally dampening effect but instead distinctively modulates ILD and presumably ITD processing in the LSO and the MSO, respectively. The major focus of the studies on GABAB receptor function in the SOC was to dissect the cellular mechanisms that contribute to changes in input efficacy

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