Role of hyperpolarization-activated conductances in the lateral superior olive: A modeling study



This modeling study examines the possible functional roles of two hyperpolarization-activated conductances in lateral superior olive (LSO) principal neurons. Inputs of these LSO neurons are transformed into an output, which provides a firing-rate code for a certain interaural sound intensity difference (IID) range. Recent experimental studies have found pharmacological evidence for the presence of both the GKIR conductance as well as the inwardly rectifying outward GKIR conductance in the LSO. We addressed the question of how these conductances influence the dynamic range (IID versus firing rate). We used computer simulations of both a point-neuron model and a two-compartmental model to investigate this issue, and to determine the role of these conductances in setting the dynamic range of these neurons. The width of the dynamic regime, the frequency-current (f-I) function, first-spike latency, subthreshold oscillations and the interplay between the two hyperpolarization activated conductances are discussed in detail. The in vivo non-monotonic IID-firing rate function in a subpopulation of LSO neurons is in good correspondence with our simulation predictions. Two compartmental model simulation results suggest segregation of Gh and GKIR conductances on different compartments, as this spatial configuration could explain certain experimental results.


hyperpolarization activated currents Ih IKIR LSO interaural sound intensity difference rate code dynamic width type I neuron type II neuron 


  1. Adam T, Finlayson P, Schwarz D (2001) Membrane properties of principal neurons of lateral superior olive. J Neurophysiol 86(2): 922–934.Google Scholar
  2. Adam T, Schwarz D, Finlayson P (1999) Firing properties of choppers and delay neurons in the lateral superior olive of the rat. Exp. Brain Res. 124(4): 489–502.Google Scholar
  3. Bal R, Oertel D (2000) Hyperpolarization-activated, mixed-cation current I h in octopus cells of the mammalian cochlear nucleus. J. Neurophysiol 84(2): 806–817.Google Scholar
  4. Banks M, Sachs M (1991) Regularity analysis in a compartmental model of chopper units in the anteroventral cochlear nucleus. J. Neurophysiol 65(3): 606–629.Google Scholar
  5. Bickmeyer U, Heine M, Manzke T, Richter D (2002) Differential modulation of I(h) by 5-HT receptors in mouse CA1 hippocampal neurons. Eur. J. Neuroscience 16(2): 209–218.Google Scholar
  6. Borisyuk A, Semple M, Rinzel J. (2002) Adaptation and inhibition underlie responses to time-varying interaural phase cues in a model of inferior colliculus neurons. J. Neurophysiol 88(4): 2134–2146.Google Scholar
  7. Chance F, Abbott L, Reyes A (2002) Gain modulation from background synaptic input. Neuron 35(4): 773–782.Google Scholar
  8. Connor J, Walter D, McKown R (1977) Neural repetitive firing: modifications of the Hodgkin-Huxley axon suggested by experimental results of crustacean axons. Biophys. J. 18(1): 81–102.Google Scholar
  9. Desjardins A, Li Y, Reinker S, Miura R, Neuman R (2003) The influences of Ih on temporal summation in hippocampal CA1 pyramidal neurons: A modeling study. J. Comput. Neurosci 15(2): 131–142.Google Scholar
  10. Doiron B, Laing C, Longtin A, Maler L (2002) Ghostbursting: a novel neuronal burst mechanism. J. Comput. Neuroscience 12(1): 5–25.Google Scholar
  11. Hooper S, Buchman E, Hobbs K (2002) A computational role for slow conductances: Single-neuron models that measure duration. Nat Neurosci 5(6): 552–556.Google Scholar
  12. Hutcheon B, Yarom Y (2000) Resonance, oscillation and the intrinsic frequency preferences of neurons. TINS. 23(5): 216–222.Google Scholar
  13. Izhikevich E (2000) Neural excitability, spiking and bursting. Int J. Bifurcation and Chaos 10: 1171–1266.Google Scholar
  14. Izhikevich E (2001) Resonate-and-fire neurons. Neural Networks 14: 883–894.Google Scholar
  15. Joris P (1996) Envelope coding in the lateral superior olive. II. Characteristic delays and comparison with responses in the medial superior olive. J. Neurophysiology 76(4): 2137–2156.Google Scholar
  16. Joris P, Yin T (1995) Envelope coding in the lateral superior olive. I. Sensitivity to interaural time differences. J. Neurophysiology 73(3): 1043–1062.Google Scholar
  17. Koch U, Groethe B (2003) Hyperpolarization-activated current (Ih) in the inferior colliculus: Distribution and contribution to temporal processing. J. Neurophysiol 90(6): 3679–3687.Google Scholar
  18. Ma Y, Cui J, Hu H, Pan Z (2003) Mammalian retinal bipolar cells express inwardly rectifying K+ currents (IKir) with a different distribution than that of Ih. J. Neurophysiol 90(5): 3479–3489.Google Scholar
  19. Margulis M, Tang C (1998) Temporal integration can readily switch between sublinear and supralinear summation. J. Neurophysiol 79(5): 2809–2813.Google Scholar
  20. McCormick D, Huguenard J. (1992) A model of the electrophysiological properties of thalamocortical relay neurons. J. Neurophysiol 68(4): 1384–1400.Google Scholar
  21. Migliore M, Messineo L, Ferrante M (2004) Dendritic Ih selectively blocks temporal summation of unsynchronized distal inputs in CA1 pyramidal neurons. J. Comp. Neurosci 16(1): 5–13.Google Scholar
  22. Nicolaus J, Ulinski P (1994) Functional interactions between inwardly rectifying conductances and GABA-mediated inhibition. CNS abstract.Google Scholar
  23. Park T, Klug A, Holinstat M, B. G (2004) Interaural level difference processing in the lateral superior olive and the inferior colliculus. J. Neurophysiol 92(1): 289–301.Google Scholar
  24. Pinsky P, Rinzel J. (1994) Intrinsic and network rhythmogenesis in a reduced Traub model for CA3 neurons. J. Comput. Neurosci. 1(1–2): 39–60.Google Scholar
  25. Redman S, McLachlan E, Hirst G (1987) Nonuniform passive membrane properies of rat lumbar sympathetic ganglion cells. J. Neurophysiol 57(3): 633–644.Google Scholar
  26. Reed M, Blum J. (1990) A model for the computation and encoding of azimuthal information by the lateral superior olive. J. Acoust. Soc. Am. 88(3): 1442–1453.Google Scholar
  27. Reyes A (2001) Influence of dendritic conductances on the input-output properties of neurons. Ann. Rev. Neurosci. 24: 653–675.Google Scholar
  28. Rinzel J, Ermentrout G (1989) Analysis of neural excitability and oscillations in Methods in Neuronal Modeling: From Synapses to Networks. MIT Press, Cambridge MA.Google Scholar
  29. Rush M, Rinzel J. (1995) The potassium A-current, low firing rates and rebound excitation in Hodgkin-Huxley models. Bull Math Biol. 57(6): 899–929.Google Scholar
  30. Sanes D (1990) An in vitro analysis of sound localization mechanisms in the gerbil lateral superior olive. J. Neuroscience 10(11): 3494–3506.Google Scholar
  31. Sanes D (2002) Right place at the right time. Nat Neuroscience 5(3): 187–188.Google Scholar
  32. Shapiro B, Lenherr F (1972) Hodgkin-Huxley axon. Increased modulation and linearity of response to constant current stimulus. Biophys J. 12: 1145–1175.Google Scholar
  33. St-Hilaire M, Longtin A (2004) Comparison of coding capabilities of Type I and Type II neurons. J. Comput. Neurosci. 16(3): 299–313.Google Scholar
  34. Takigawa T, Alzheimer C (1999) G protein-activated inwardly rectifying K+ (GIRK) currents in dendrites of rat neocortical pyramidal cells. J. Physiol. 517: 385–390.Google Scholar
  35. Takigawa T, Alzheimer C (2003) Interplay between activation of GIRK current and deactivation of Ih modifies temporal integration of excitatory input in CA1 pyramidal cells. J. Neurophysiol 89(4): 2238–2244.Google Scholar
  36. Takigawa T, Alzheimer C (2002) Phasic and tonic attenuation of EPSPs by inward rectifying K+ channels. J. Physiol. 539: 67–75.Google Scholar
  37. Tiesinga P (2004) Chaos-induced modulation of reliability boosts output firing rate in downstream cortical areas. Phys. Rev. E. 69(3): 031912.Google Scholar
  38. Tollin D (2003) The lateral superior olive: A functional role in sound source localization. Neuroscientist 9(2): 127–143.Google Scholar
  39. Tsuchitani C (1988) The inhibition of cat lateral superior olive unit excitatory responses to binaural tone bursts. I. The transient chopper response. J. Neurophysiol. 59(1): 164–183.Google Scholar
  40. Wessel R, Kristan W, Kleinfeld D (1999) Supralinear summation of synaptic inputs by an invertebrate neuron: Dendritic gain is mediated by an “inward rectifier” K(+) current. J. Neurosci 19(14): 5875–5888.Google Scholar
  41. Wilson C (1995) Dynamic modification of dendritic cable properties and synaptic transmission by voltage-gated potassium channels. J. Comput Neurosci 2(2): 91–115.Google Scholar
  42. Wilson C (2005) The Mechanism of Intrinsic Amplification of Hyperpolarizations and Spontaneous Bursting of Striatal Cholinergic Interneurons. Neuron 45(4): 575–585.Google Scholar
  43. Zacksenhouse M, Johnson D, Williams J, Tsuchitani C (1998) Single-Neuron Modeling of LSO Unit Responses. J. Neurophysiol. 79(6): 3098–3110.Google Scholar

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  1. 1.Department of Biophysics, Computational Neuroscience GroupKFKI Research Institute for Particle and Nuclear Physics of the Hungarian Academy of SciencesBudapestHungary

Personalised recommendations