Inhibitory Plasticity and Auditory Function

  • Robert C. Liu


The mammalian auditory system serves many functions for an ­organism throughout its life, including the spatial localization of sound sources and the recognition of behaviorally-relevant sounds. The neural circuitry underlying these various functions are not all fully elucidated, but likely involve key contributions from both subcortical as well as cortical auditory areas. While the focus has often been on the role of neural excitation within these areas, there is increasing recognition that neural inhibition and its plasticity can be just as important in shaping the function of auditory circuits.

The purpose of this chapter is to use a few of the known examples of how inhibition and inhibitory plasticity subserve the functional processing of sounds to illustrate both the advances that have been made in terms of understanding mechanisms as well as the open questions remaining. The first example deals with sound localization and the brainstem circuitry that decodes binaural spatial cues. This provides one of the most detailed auditory examples of the function of inhibitory synaptic input, how inhibitory circuitry is modified by activity during development, and what potential cellular mechanisms are critical for this plasticity. The other two examples focus on the neural coding and plasticity of behaviorally relevant sounds at the cortical level. One centers on how inhibition shapes the selectivity of individual neurons for frequency modulated sounds during development, and the other on its hypothesized role in the population representation of a communication call in adults. While the cellular mechanisms underlying inhibitory plasticity are less clear in these latter cases, taken all together these examples demonstrate the importance and pervasiveness of inhibition in the functional processing of sounds.


Local Field Potential Interaural Timing Difference Auditory Nerve Fiber Direction Selectivity Interaural Level Difference 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Banks MI, Smith PH (1992) Intracellular recordings from neurobiotin-labeled cells in brain slices of the rat medial nucleus of the trapezoid body. J Neurosci 12:2819–2837.PubMedGoogle Scholar
  2. Batra R, Kuwada S, Fitzpatrick DC (1997) Sensitivity to interaural temporal disparities of low- and high-frequency neurons in the superior olivary complex. II. Coincidence detection. J Neurophysiol 78:1237–1247.PubMedGoogle Scholar
  3. Blackburn CC, Sachs MB (1989) Classification of unit types in the anteroventral cochlear nucleus: PST histograms and regularity analysis. J Neurophysiol 62:1303–1329.PubMedGoogle Scholar
  4. Brand A, Behrend O, Marquardt T, McAlpine D, Grothe B (2002) Precise inhibition is essential for microsecond interaural time difference coding. Nature 417:543–547.PubMedCrossRefGoogle Scholar
  5. Brown P (1976) Vocal communication in the pallid bat, Antrozous pallidus. Z Tierpsychol 41:34–54.PubMedCrossRefGoogle Scholar
  6. Cant NB, Casseday JH (1986) Projections from the anteroventral cochlear nucleus to the lateral and medial superior olivary nuclei. J Comp Neurol 247:457–476.PubMedCrossRefGoogle Scholar
  7. Cant NB, Hyson RL (1992) Projections from the lateral nucleus of the trapezoid body to the medial superior olivary nucleus in the gerbil. Hear Res 58:26–34.PubMedCrossRefGoogle Scholar
  8. Carr CE, Konishi M (1988) Axonal delay lines for time measurement in the owl’s brainstem. Proc Natl Acad Sci U S A 85:8311–8315.PubMedCrossRefGoogle Scholar
  9. Chang EH, Kotak VC, Sanes DH (2003) Long-term depression of synaptic inhibition is expressed postsynaptically in the developing auditory system. J Neurophysiol 90:1479–1488.PubMedCrossRefGoogle Scholar
  10. DeWeese MR, Zador AM (2006) Non-Gaussian membrane potential dynamics imply sparse, synchronous activity in auditory cortex. J Neurosci 26:12206–12218.PubMedCrossRefGoogle Scholar
  11. Ehret G, Koch M, Haack B, Markl H (1987) Sex and parental experience determine the onset of an instinctive behavior in mice. Naturwissenschaften 74:47.PubMedCrossRefGoogle Scholar
  12. Fuzessery ZM (1996) Monaural and binaural spectral cues created by the external ears of the pallid bat. Hear Res 95:1–17.PubMedCrossRefGoogle Scholar
  13. Gaiarsa JL, Caillard O, Ben-Ari Y (2002) Long-term plasticity at GABAergic and glycinergic synapses: mechanisms and functional significance. Trends Neurosci 25:564–570.PubMedCrossRefGoogle Scholar
  14. Galindo-Leon EE, Lin FG, Liu RC (2009) Inhibitory plasticity in a lateral band improves cortical detection of natural vocalizations. Neuron 62:705–716.PubMedCrossRefGoogle Scholar
  15. Geisler CD (1998) From sound to synapse : physiology of the mammalian ear. New York: Oxford University Press.Google Scholar
  16. Gillespie DC, Kim G, Kandler K (2005) Inhibitory synapses in the developing auditory system are glutamatergic. Nat Neurosci 8:332–338.PubMedCrossRefGoogle Scholar
  17. Grothe B (2003) New roles for synaptic inhibition in sound localization. Nat Rev Neurosci 4:540–550.PubMedCrossRefGoogle Scholar
  18. Grothe B, Sanes DH (1993) Bilateral inhibition by glycinergic afferents in the medial superior olive. J Neurophysiol 69:1192–1196.PubMedGoogle Scholar
  19. Grothe B, Park TJ (1998) Sensitivity to interaural time differences in the medial superior olive of a small mammal, the Mexican free-tailed bat. J Neurosci 18:6608–6622.PubMedGoogle Scholar
  20. Grothe B, Park TJ, Schuller G (1997) Medial superior olive in the free-tailed bat: response to pure tones and amplitude-modulated tones. J Neurophysiol 77:1553–1565.PubMedGoogle Scholar
  21. Haack B, Markl H, Ehret G (1983) Sound communication between parents and offspring. In: The auditory psychobiology of the mouse (Willott JF, ed), pp 57–97. Springfield, IL: Charles C. Thomas.Google Scholar
  22. Jeffress LA (1948) A place theory of sound localization. J Comp Physiol Psychol 41:35–39.PubMedCrossRefGoogle Scholar
  23. Joris PX, Carney LH, Smith PH, Yin TC (1994) Enhancement of neural synchronization in the anteroventral cochlear nucleus. I. Responses to tones at the characteristic frequency. J Neurophysiol 71:1022–1036.PubMedGoogle Scholar
  24. Kandler K, Friauf E (1995) Development of glycinergic and glutamatergic synaptic transmission in the auditory brainstem of perinatal rats. J Neurosci 15:6890–6904.PubMedGoogle Scholar
  25. Kandler K, Clause A, Noh J (2009) Tonotopic reorganization of developing auditory brainstem circuits. Nat Neurosci 12:711–717.PubMedCrossRefGoogle Scholar
  26. Kanwal JS, Matsumura S, Ohlemiller K, Suga N (1994) Analysis of acoustic elements and syntax in communication sounds emitted by mustached bats. J Acoust Soc Am 96:1229–1254.PubMedCrossRefGoogle Scholar
  27. Kapfer C, Seidl AH, Schweizer H, Grothe B (2002) Experience-dependent refinement of inhibitory inputs to auditory coincidence-detector neurons. Nat Neurosci 5:247–253.PubMedCrossRefGoogle Scholar
  28. Kim G, Kandler K (2003) Elimination and strengthening of glycinergic/GABAergic connections during tonotopic map formation. Nat Neurosci 6:282–290.PubMedCrossRefGoogle Scholar
  29. Kotak VC, Sanes DH (2000) Long-lasting inhibitory synaptic depression is age- and calcium-dependent. J Neurosci 20:5820–5826.PubMedGoogle Scholar
  30. Kotak VC, DiMattina C, Sanes DH (2001) GABA(B) and Trk receptor signaling mediates long-lasting inhibitory synaptic depression. J Neurophysiol 86:536–540.PubMedGoogle Scholar
  31. Kotak VC, Korada S, Schwartz IR, Sanes DH (1998) A developmental shift from GABAergic to glycinergic transmission in the central auditory system. J Neurosci 18:4646–4655.PubMedGoogle Scholar
  32. Kullmann PH, Kandler K (2001) Glycinergic/GABAergic synapses in the lateral superior olive are excitatory in neonatal C57Bl/6J mice. Brain Res Dev Brain Res 131:143–147.PubMedCrossRefGoogle Scholar
  33. Kullmann PH, Kandler K (2008) Dendritic Ca2+ responses in neonatal lateral superior olive neurons elicited by glycinergic/GABAergic synapses and action potentials. Neuroscience 154:338–345.PubMedCrossRefGoogle Scholar
  34. Kullmann PH, Ene FA, Kandler K (2002) Glycinergic and GABAergic calcium responses in the developing lateral superior olive. Eur J Neurosci 15:1093–1104.PubMedCrossRefGoogle Scholar
  35. Kuwabara N, Zook JM (1992) Projections to the medial superior olive from the medial and lateral nuclei of the trapezoid body in rodents and bats. J Comp Neurol 324:522–538.PubMedCrossRefGoogle Scholar
  36. Lindblom BEF, Studdert-Kennedy M (1967) On the role of formant transitions in vowel recognition. J Acoust Soc Am 42:830–843.PubMedCrossRefGoogle Scholar
  37. Liu RC, Schreiner CE (2007) Auditory cortical detection and discrimination correlates with communicative significance. PLoS Biol 5:e173.PubMedCrossRefGoogle Scholar
  38. Liu RC, Linden JF, Schreiner CE (2006) Improved cortical entrainment to infant communication calls in mothers compared with virgin mice. Eur J Neurosci 23:3087–3097.PubMedCrossRefGoogle Scholar
  39. Liu RC, Miller KD, Merzenich MM, Schreiner CE (2003) Acoustic variability and distinguishability among mouse ultrasound vocalizations. J Acoust Soc Am 114:3412–3422.PubMedCrossRefGoogle Scholar
  40. Logothetis NK (2003) The underpinnings of the BOLD functional magnetic resonance imaging signal. J Neurosci 23:3963–3971.PubMedGoogle Scholar
  41. Luscher B, Keller CA (2004) Regulation of GABAA receptor trafficking, channel activity, and functional plasticity of inhibitory synapses. Pharmacol Ther 102:195–221.PubMedCrossRefGoogle Scholar
  42. Magnusson AK, Park TJ, Pecka M, Grothe B, Koch U (2008) Retrograde GABA signaling adjusts sound localization by balancing excitation and inhibition in the brainstem. Neuron 59:125–137.PubMedCrossRefGoogle Scholar
  43. McAlpine D, Grothe B (2003) Sound localization and delay lines–do mammals fit the model? Trends Neurosci 26:347–350.PubMedCrossRefGoogle Scholar
  44. Miranda JA, Liu RC (2009) Dissecting natural sensory plasticity: hormones and experience in a maternal context. Hear Res 252:21–28.PubMedCrossRefGoogle Scholar
  45. Overholt EM, Rubel EW, Hyson RL (1992) A circuit for coding interaural time differences in the chick brainstem. J Neurosci 12:1698–1708.PubMedGoogle Scholar
  46. Pola YV, Snowdon CT (1975) The vocalizations of pygmy marmosets (Cebuella pygmaea). Anim Behav 23:826–842.PubMedCrossRefGoogle Scholar
  47. Poulet JF, Petersen CC (2008) Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice. Nature 454:881–885.PubMedCrossRefGoogle Scholar
  48. Razak KA, Fuzessery ZM (2002) Functional organization of the pallid bat auditory cortex: emphasis on binaural organization. J Neurophysiol 87:72–86.PubMedGoogle Scholar
  49. Razak KA, Fuzessery ZM (2006) Neural mechanisms underlying selectivity for the rate and direction of frequency-modulated sweeps in the auditory cortex of the pallid bat. J Neurophysiol 96:1303–1319.PubMedCrossRefGoogle Scholar
  50. Razak KA, Fuzessery ZM (2007) Development of inhibitory mechanisms underlying selectivity for the rate and direction of frequency-modulated sweeps in the auditory cortex. J Neurosci 27:1769–1781.PubMedCrossRefGoogle Scholar
  51. Razak KA, Richardson MD, Fuzessery ZM (2008) Experience is required for the maintenance and refinement of FM sweep selectivity in the developing auditory cortex. Proc Natl Acad Sci U S A 105:4465–4470.PubMedCrossRefGoogle Scholar
  52. Rice JJ, May BJ, Spirou GA, Young ED (1992) Pinna-based spectral cues for sound localization in cat. Hear Res 58:132–152.PubMedCrossRefGoogle Scholar
  53. Rietzel HJ, Friauf E (1998) Neuron types in the rat lateral superior olive and developmental changes in the complexity of their dendritic arbors. J Comp Neurol 390:20–40.PubMedCrossRefGoogle Scholar
  54. Rose JE, Brugge JF, Anderson DJ, Hind JE (1967) Phase-locked response to low-frequency tones in single auditory nerve fibers of the squirrel monkey. J Neurophysiol 30:769–793.PubMedGoogle Scholar
  55. Sanes DH, Rubel EW (1988) The ontogeny of inhibition and excitation in the gerbil lateral superior olive. J Neurosci 8:682–700.PubMedGoogle Scholar
  56. Sanes DH, Siverls V (1991) Development and specificity of inhibitory terminal arborizations in the central nervous system. J Neurobiol 22:837–854.PubMedCrossRefGoogle Scholar
  57. Sanes DH, Takacs C (1993) Activity-dependent refinement of inhibitory connections. Eur J Neurosci 5:570–574.PubMedCrossRefGoogle Scholar
  58. Sanes DH, Song J, Tyson J (1992a) Refinement of dendritic arbors along the tonotopic axis of the gerbil lateral superior olive. Brain Res Dev Brain Res 67:47–55.PubMedCrossRefGoogle Scholar
  59. Sanes DH, Markowitz S, Bernstein J, Wardlow J (1992b) The influence of inhibitory afferents on the development of postsynaptic dendritic arbors. J Comp Neurol 321:637–644.PubMedCrossRefGoogle Scholar
  60. Satzler K, Sohl LF, Bollmann JH, Borst JG, Frotscher M, Sakmann B, Lubke JH (2002) Three-dimensional reconstruction of a calyx of Held and its postsynaptic principal neuron in the medial nucleus of the trapezoid body. J Neurosci 22:10567–10579.PubMedGoogle Scholar
  61. Seidl AH, Grothe B (2005) Development of sound localization mechanisms in the mongolian gerbil is shaped by early acoustic experience. J Neurophysiol 94:1028–1036.PubMedCrossRefGoogle Scholar
  62. Sewell GD (1970) Ultrasonic communication in rodents. Nature 227:410.PubMedCrossRefGoogle Scholar
  63. Smith JC (1976) Responses of adult mice to models of infant calls. J Comp Physiol Psychol 90:1105–1115.CrossRefGoogle Scholar
  64. Smith PH, Joris PX, Yin TC (1998) Anatomy and physiology of principal cells of the medial nucleus of the trapezoid body (MNTB) of the cat. J Neurophysiol 79:3127–3142.PubMedGoogle Scholar
  65. Smith PH, Joris PX, Carney LH, Yin TCT (1991) Projections of physiologically characterized globular bushy cell axons from the cochlear nucleus of the cat. J Comp Neurol 304:387–407.PubMedCrossRefGoogle Scholar
  66. Suga N (1965) Functional properties of auditory neurones in the cortex of echo-locating bats. J Physiol 181:671–700.PubMedGoogle Scholar
  67. Tollin DJ, Yin TC (2002a) The coding of spatial location by single units in the lateral superior olive of the cat. II. The determinants of spatial receptive fields in azimuth. J Neurosci 22:1468–1479.PubMedGoogle Scholar
  68. Tollin DJ, Yin TC (2002b) The coding of spatial location by single units in the lateral superior olive of the cat. I. Spatial receptive fields in azimuth. J Neurosci 22:1454–1467.PubMedGoogle Scholar
  69. Walsh EJ, McGee J (1988) Rhythmic discharge properties of caudal cochlear nucleus neurons during postnatal development in cats. Hear Res 36:233–247.PubMedCrossRefGoogle Scholar
  70. Wang X (2000) On cortical coding of vocal communication sounds in primates. Proc Natl Acad Sci U S A 97:11843–11849.PubMedCrossRefGoogle Scholar
  71. Werthat F, Alexandrova O, Grothe B, Koch U (2008) Experience-dependent refinement of the inhibitory axons projecting to the medial superior olive. Dev Neurobiol 68:1454–1462.PubMedCrossRefGoogle Scholar
  72. Wightman FL, Kistler DJ (1993) Sound Localization. In: Human Psychophysics (Yost WA, Popper AN, Fay RR, eds), pp 155–192. New York, NY: Springer.Google Scholar
  73. Withington-Wray DJ, Binns KE, Dhanjal SS, Brickley SG, Keating MJ (1990) The maturation of the superior collicular map of auditory space in the guinea pig is disrupted by developmental auditory deprivation. Eur J Neurosci 2:693–703.PubMedCrossRefGoogle Scholar
  74. Yates GK, Robertson D, Johnstone BM (1985) Very rapid adaptation in the guinea pig auditory nerve. Hear Res 17:1–12.PubMedCrossRefGoogle Scholar
  75. Yin TC, Chan JC (1990) Interaural time sensitivity in medial superior olive of cat. J Neurophysiol 64:465–488.PubMedGoogle Scholar
  76. Zhang LI, Tan AY, Schreiner CE, Merzenich MM (2003) Topography and synaptic shaping of direction selectivity in primary auditory cortex. Nature 424:201–205.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of BiologyEmory UniversityAtlantaUSA

Personalised recommendations