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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References
Carandini, M. & Heeger, D.J. Normalization as a canonical neural computation. Nat. Rev. Neurosci. 13, 51–62 (2012).
Maier, J.K. et al. Adaptive coding is constrained to midline locations in a spatial listening task. J. Neurophysiol. 108, 1856–1868 (2012).
Ingham, N.J. & McAlpine, D. Spike-frequency adaptation in the inferior colliculus. J. Neurophysiol. 91, 632–645 (2004).
Sanes, D.H., Malone, B.J. & Semple, M.N. Role of synaptic inhibition in processing of dynamic binaural level stimuli. J. Neurosci. 18, 794–803 (1998).
Dahmen, J.C., Keating, P., Nodal, F.R., Schulz, A.L. & King, A.J. Adaptation to stimulus statistics in the perception and neural representation of auditory space. Neuron 66, 937–948 (2010).
Phillips, D.P. & Hall, S.E. Psychophysical evidence for adaptation of central auditory processors for interaural differences in time and level. Hear. Res. 202, 188–199 (2005).
Park, T.J., Brand, A., Koch, U., Ikebuchi, M. & Grothe, B. Dynamic changes in level influence spatial coding in the lateral superior olive. Hear. Res. 238, 58–67 (2008).
Magnusson, A.K., Park, T.J., Pecka, M., Grothe, B. & Koch, U. Retrograde GABA signaling adjusts sound localization by balancing excitation and inhibition in the brainstem. Neuron 59, 125–137 (2008).
Wightman, F.L. & Kistler, D.J. The dominant role of low-frequency interaural time differences in sound localization. J. Acoust. Soc. Am. 91, 1648–1661 (1992).
Grothe, B. & Sanes, D.H. Synaptic inhibition influences the temporal coding properties of medial superior olivary neurons: an in vitro study. J. Neurosci. 14, 1701–1709 (1994).
Magnusson, A.K., Kapfer, C., Grothe, B. & Koch, U. Maturation of glycinergic inhibition in the gerbil medial superior olive after hearing onset. J. Physiol. (Lond.) 568, 497–512 (2005).
Pecka, M., Brand, A., Behrend, O. & Grothe, B. Interaural time difference processing in the mammalian medial superior olive: the role of glycinergic inhibition. J. Neurosci. 28, 6914–6925 (2008).
Brand, A., Behrend, O., Marquardt, T., McAlpine, D. & Grothe, B. Precise inhibition is essential for microsecond interaural time difference coding. Nature 417, 543–547 (2002).
Couchman, K., Grothe, B. & Felmy, F. Functional localization of neurotransmitter receptors and synaptic inputs to mature neurons of the medial superior olive. J. Neurophysiol. 107, 1186–1198 (2012).
Smith, A.J., Owens, S. & Forsythe, I.D. Characterisation of inhibitory and excitatory postsynaptic currents of the rat medial superior olive. J. Physiol. (Lond.) 529, 681–698 (2000).
Fischl, M.J., Combs, T.D., Klug, A., Grothe, B. & Burger, R.M. Modulation of synaptic input by GABAB receptors improves coincidence detection for computation of sound location. J. Physiol. (Lond.) 590, 3047–3066 (2012).
Hassfurth, B., Grothe, B. & Koch, U. The mammalian interaural time difference detection circuit is differentially controlled by GABAB receptors during development. J. Neurosci. 30, 9715–9727 (2010).
Grothe, B. New roles for synaptic inhibition in sound localization. Nat. Rev. Neurosci. 4, 540–550 (2003).
McAlpine, D. & Grothe, B. Sound localization and delay lines—do mammals fit the model? Trends Neurosci. 26, 347–350 (2003).
Ito, T. & Oliver, D.L. Origins of glutamatergic terminals in the inferior colliculus identified by retrograde transport and expression of VGLUT1 and VGLUT2 genes. Front. Neuroanat. 4, 135 (2010).
Roberts, R.C. & Ribak, C.E. GABAergic neurons and axon terminals in the brainstem auditory nuclei of the gerbil. J. Comp. Neurol. 258, 267–280 (1987).
Kuwabara, N. & Zook, J.M. Local collateral projections from the medial superior olive to the superior paraolivary nucleus in the gerbil. Brain Res. 846, 59–71 (1999).
Behrend, O., Brand, A., Kapfer, C. & Grothe, B. Auditory response properties in the superior paraolivary nucleus of the gerbil. J. Neurophysiol. 87, 2915–2928 (2002).
Kopp-Scheinpflug, C. et al. The sound of silence: ionic mechanisms encoding sound termination. Neuron 71, 911–925 (2011).
Felix, R.A., Fridberger, A., Leijon, S., Berrebi, A.S. & Magnusson, A.K. Sound rhythms are encoded by postinhibitory rebound spiking in the superior paraolivary nucleus. J. Neurosci. 31, 12566–12578 (2011).
Dehmel, S., Kopp-Scheinpflug, C., Dorrscheidt, G.J. & Rubsamen, R. Electrophysiological characterization of the superior paraolivary nucleus in the Mongolian gerbil. Hear. Res. 172, 18–36 (2002).
Grothe, B., Pecka, M. & McAlpine, D. Mechanisms of sound localization in mammals. Physiol. Rev. 90, 983–1012 (2010).
Vigneault-MacLean, B.K., Hall, S.E. & Phillips, D.P. The effects of lateralized adaptors on lateral position judgements of tones within and across frequency channels. Hear. Res. 224, 93–100 (2007).
Kashino, M. & Nishida, S. Adaptation in the processing of interaural time differences revealed by the auditory localization aftereffect. J. Acoust. Soc. Am. 103, 3597–3604 (1998).
Goldberg, J.M. & Brown, P.B. Response of binaural neurons of dog superior olivary complex to dichotic tonal stimuli: some physiological mechanisms of sound localization. J. Neurophysiol. 32, 613–636 (1969).
Yin, T.C. & Chan, J.C. Interaural time sensitivity in medial superior olive of cat. J. Neurophysiol. 64, 465–488 (1990).
Getzmann, S. Spatial discrimination of sound sources in the horizontal plane following an adapter sound. Hear. Res. 191, 14–20 (2004).
Wark, B., Lundstrom, B.N. & Fairhall, A. Sensory adaptation. Curr. Opin. Neurobiol. 17, 423–429 (2007).
Robinson, B.L. & McAlpine, D. Gain control mechanisms in the auditory pathway. Curr. Opin. Neurobiol. 19, 402–407 (2009).
Wen, B., Wang, G.I., Dean, I. & Delgutte, B. Dynamic range adaptation to sound level statistics in the auditory nerve. J. Neurosci. 29, 13797–13808 (2009).
Wen, B., Wang, G.I., Dean, I. & Delgutte, B. Time course of dynamic range adaptation in the auditory nerve. J. Neurophysiol. 108, 69–82 (2012).
May, B.J. & Sachs, M.B. Dynamic range of neural rate responses in the ventral cochlear nucleus of awake cats. J. Neurophysiol. 68, 1589–1602 (1992).
Park, T.J., Grothe, B., Pollak, G.D., Schuller, G. & Koch, U. Neural delays shape selectivity to interaural intensity differences in the lateral superior olive. J. Neurosci. 16, 6554–6566 (1996).
Pecka, M., Siveke, I., Grothe, B. & Lesica, N.A. Enhancement of ITD coding within the initial stages of the auditory pathway. J. Neurophysiol. 103, 38–46 (2010).
Heeger, D.J. Normalization of cell responses in cat striate cortex. Vis. Neurosci. 9, 181–197 (1992).
Carandini, M., Heeger, D.J. & Movshon, J.A. Linearity and normalization in simple cells of the macaque primary visual cortex. J. Neurosci. 17, 8621–8644 (1997).
Pouille, F., Marin-Burgin, A., Adesnik, H., Atallah, B.V. & Scanziani, M. Input normalization by global feedforward inhibition expands cortical dynamic range. Nat. Neurosci. 12, 1577–1585 (2009).
Rabinowitz, N.C., Willmore, B.D.B., Schnupp, J.W.H. & King, A.J. Contrast gain control in auditory cortex. Neuron 70, 1178–1191 (2011).
Khouri, L., Lesica, N.A. & Grothe, B. Impaired auditory temporal selectivity in the inferior colliculus of aged mongolian gerbils. J. Neurosci. 31, 9958–9970 (2011).
Siveke, I., Leibold, C., Schiller, E. & Grothe, B. Adaptation of binaural processing in the adult brainstem induced by ambient noise. J. Neurosci. 32, 462–473 (2012).
Siveke, I., Pecka, M., Seidl, A.H., Baudoux, S. & Grothe, B. Binaural response properties of low-frequency neurons in the gerbil dorsal nucleus of the lateral lemniscus. J. Neurophysiol. 96, 1425–1440 (2006).
Kuwada, S. & Yin, T.C. Binaural interaction in low-frequency neurons in inferior colliculus of the cat. I. Effects of long interaural delays, intensity, and repetition rate on interaural delay function. J. Neurophysiol. 50, 981–999 (1983).
Mardia, K. Statistics of Directional Data (Academic, London, 1972).
Couchman, K., Grothe, B. & Felmy, F. Medial superior olivary neurons receive surprisingly few excitatory and inhibitory inputs with balanced strength and short-term dynamics. J. Neurosci. 30, 17111–17121 (2010).
Ford, M.C., Grothe, B. & Klug, A. Fenestration of the calyx of Held occurs sequentially along the tonotopic axis, is influenced by afferent activity, and facilitates glutamate clearance. J. Comp. Neurol. 514, 92–106 (2009).
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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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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DOI: https://doi.org/10.1038/nn.3548
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