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Adaptation in sound localization: from GABAB receptor–mediated synaptic modulation to perception

Abstract

Across all sensory modalities, the effect of context-dependent neural adaptation can be observed at every level, from receptors to perception. Nonetheless, it has long been assumed that the processing of interaural time differences, which is the primary cue for sound localization, is nonadaptive, as its outputs are mapped directly onto a hard-wired representation of space. Here we present evidence derived from in vitro and in vivo experiments in gerbils indicating that the coincidence-detector neurons in the medial superior olive modulate their sensitivity to interaural time differences through a rapid, GABAB receptor–mediated feedback mechanism. We show that this mechanism provides a gain control in the form of output normalization, which influences the neuronal population code of auditory space. Furthermore, psychophysical tests showed that the paradigm used to evoke neuronal GABAB receptor–mediated adaptation causes the perceptual shift in sound localization in humans that was expected on the basis of our physiological results in gerbils.

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Figure 1: GABAB receptor–dependent modulation of neuronal responses in the MSO in vivo.
Figure 2: GABAB receptor–mediated modulation of ITD sensitivity in the MSO.
Figure 3: GABAB receptor–mediated modulation of basal synaptic strength measured in vitro in acute brain slices.
Figure 4: Prior stimuli induce adaptation in the MSO.
Figure 5: Blocking GABAB receptor–mediated inhibition decreases the stimulus-induced adaptation in the MSO.
Figure 6: The SPN provides GABAergic input to the MSO.
Figure 7: GABAB receptor modulation and acoustic adaptation change the MSO population code.
Figure 8: Adaptation to prior stimuli in human ITD-based sound lateralization.

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Acknowledgements

The in vivo experiments and anatomical studies were funded by Deutsche Forschungsgemeinschaft (DFG) grant DFG-SFB870 TP-B02, the in vitro recordings were funded by DFG-SFB870 TP-B01 and the Alexander von Humboldt Foundation, and the psychophysical study was funded by the Bundesministerium für Bildung und Forschung (BMBF)-funded German Center for Vertigo and Balance Disorders (IFB). We thank T. Jennings and H. Gleiss for help with stimulus programming and P. Hardy for helpful suggestions concerning the text.

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A.S. performed the in vivo experiments, analyzed the data and wrote the relevant parts of the manuscript. M.H.M. performed the in vitro experiments, analyzed the data and wrote the relevant parts of the manuscript. A.L. performed the psychophysical experiments, analyzed the data and wrote the relevant parts of the manuscript. M.C.F. performed the fiber tracing experiments, analyzed the data and wrote the relevant parts of the manuscript. O.A. performed the immunohistochemistry experiments and confocal microscopy, analyzed the data and wrote the relevant parts of the manuscript. F.F. supervised the in vitro experiments. M.P. supervised the adaptation (in vivo and psychophysical) experiments and wrote parts of the manuscript. I.S. and B.G. supervised the project and wrote the manuscript.

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Correspondence to Benedikt Grothe.

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Stange, A., Myoga, M., Lingner, A. et al. Adaptation in sound localization: from GABAB receptor–mediated synaptic modulation to perception. Nat Neurosci 16, 1840–1847 (2013). https://doi.org/10.1038/nn.3548

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