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Control of submillisecond synaptic timing in binaural coincidence detectors by Kv1 channels

Nature Neuroscience volume 13, pages 601–609 (2010)Cite this article

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Abstract

Neurons in the medial superior olive process sound-localization cues via binaural coincidence detection, in which excitatory synaptic inputs from each ear are segregated onto different branches of a bipolar dendritic structure and summed at the soma and axon with submillisecond time resolution. Although synaptic timing and dynamics critically shape this computation, synaptic interactions with intrinsic ion channels have received less attention. Using paired somatic and dendritic patch-clamp recordings in gerbil brainstem slices together with compartmental modeling, we found that activation of Kv1 channels by dendritic excitatory postsynaptic potentials (EPSPs) accelerated membrane repolarization in a voltage-dependent manner and actively improved the time resolution of synaptic integration. We found that a somatically biased gradient of Kv1 channels underlies the degree of compensation for passive cable filtering during propagation of EPSPs in dendrites. Thus, both the spatial distribution and properties of Kv1 channels are important for preserving binaural synaptic timing.

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Figure 1: Propagation of simulated EPSPs from the dendrites to the soma in MSO neurons.
Figure 2: The shape of EPSPs is stable regardless of propagation distance.
Figure 3: A DTX-sensitive conductance mediates EPSP sharpening.
Figure 4: Characterization of IK-LVA in outside-out patches.
Figure 5: Relative timing of IK-LVA and sEPSPs in whole-cell recordings at 35 °C.
Figure 6: VDS for dendritic and somatic EPSC injection in a compartmental model of the MSO.
Figure 7: Spatial effects of VDS in an MSO neuron model.
Figure 8: Spatio-temporal dynamics of membrane potential and IK-LVA for bilateral ITD-like distal inputs (750 Hz).

References

  1. Caporale, N. & Dan, Y. Spike timing–dependent plasticity: a Hebbian learning rule. Annu. Rev. Neurosci. 31, 25–46 (2008).

    Article  CAS  Google Scholar 

  2. Mauk, M.D. & Buonomano, D.V. The neural basis of temporal processing. Annu. Rev. Neurosci. 27, 307–340 (2004).

    Article  CAS  Google Scholar 

  3. Rinzel, J. & Rall, W. Transient response in a dendritic neuron model for current injected at one branch. Biophys. J. 14, 759–790 (1974).

    Article  CAS  Google Scholar 

  4. Segev, I. & London, M. Untangling dendrites with quantitative models. Science 290, 744–750 (2000).

    Article  CAS  Google Scholar 

  5. Carr, C.E. Processing of temporal information in the brain. Annu. Rev. Neurosci. 16, 223–243 (1993).

    Article  CAS  Google Scholar 

  6. Grothe, B. Sensory systems: New roles for synaptic inhibition in sound localization. Nat. Rev. Neurosci. 4, 540–550 (2003).

    Article  CAS  Google Scholar 

  7. Joris, P. & Yin, T. A matter of time: internal delays in binaural processing. Trends Neurosci. 30, 70–78 (2007).

    Article  CAS  Google Scholar 

  8. Stotler, W.A. An experimental study of the cells and connections of the superior olivary complex of the cat. J. Comp. Neurol. 98, 401–431 (1953).

    Article  CAS  Google Scholar 

  9. Scott, L.L., Mathews, P.J. & Golding, N.L. Posthearing developmental refinement of temporal processing in principal neurons of the medial superior olive. J. Neurosci. 25, 7887–7895 (2005).

    Article  CAS  Google Scholar 

  10. Scott, L.L., Hage, T.A. & Golding, N.L. Weak action potential backpropagation is associated with high-frequency axonal firing capability in principal neurons of the gerbil medial superior olive. J. Physiol. (Lond.) 583, 647–661 (2007).

    Article  CAS  Google Scholar 

  11. Agmon-Snir, H., Carr, C.E. & Rinzel, J. The role of dendrites in auditory coincidence detection. Nature 393, 268–272 (1998).

    Article  CAS  Google Scholar 

  12. Dasika, V.K., White, J.A. & Colburn, H.S. Simple models show the general advantages of dendrites in coincidence detection. J. Neurophysiol. 97, 3449–3459 (2007).

    Article  Google Scholar 

  13. Grau-Serrat, V., Carr, C.E. & Simon, J.Z. Modeling coincidence detection in nucleus laminaris. Biol. Cybern. 89, 388–396 (2003).

    Article  Google Scholar 

  14. Zhou, Y., Carney, L.H. & Colburn, H.S. A model for interaural time difference sensitivity in the medial superior olive: interaction of excitatory and inhibitory synaptic inputs, channel dynamics and cellular morphology. J. Neurosci. 25, 3046–3058 (2005).

    Article  CAS  Google Scholar 

  15. Svirskis, G., Kotak, V., Sanes, D.H. & Rinzel, J. Enhancement of signal-to-noise ratio and phase locking for small inputs by a low-threshold outward current in auditory neurons. J. Neurosci. 22, 11019–11025 (2002).

    Article  CAS  Google Scholar 

  16. Scott, L.L., Mathews, P.J. & Golding, N.L. Perisomatic voltage-gated sodium channels actively maintain linear synaptic integration in principal neurons of the medial superior olive. J. Neurosci. 30, 2039–2050 (2010).

    Article  CAS  Google Scholar 

  17. Martina, M., Vida, I. & Jonas, P. Distal initiation and active propagation of action potentials in interneuron dendrites. Science 287, 295–300 (2000).

    Article  CAS  Google Scholar 

  18. Rothman, J.S. & Manis, P.B. Kinetic analyses of three distinct potassium conductances in ventral cochlear nucleus neurons. J. Neurophysiol. 89, 3083–3096 (2003).

    Article  CAS  Google Scholar 

  19. Grissmer, S. et al. Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv1.1, 1.2, 1.3, 1.5 and 3.1, stably expressed in mammalian cell lines. Mol. Pharmacol. 45, 1227–1234 (1994).

    CAS  PubMed  Google Scholar 

  20. Hopkins, W.F., Allen, M.L., Houamed, K.M. & Tempel, B.L. Properties of voltage-gated K+ currents expressed in Xenopus oocytes by mKv1.1, mKv1.2 and their heteromultimers as revealed by mutagenesis of the dendrotoxin-binding site in mKv1.1. Pflugers Arch. 428, 382–390 (1994).

    Article  CAS  Google Scholar 

  21. Stühmer, W. et al. Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain. EMBO J. 8, 3235–3244 (1989).

    Article  Google Scholar 

  22. Allen, P.D., Schmuck, N., Ison, J.R. & Walton, J.P. Kv1.1 channel subunits are not necessary for high temporal acuity in behavioral and electrophysiological gap detection. Hear. Res. 246, 52–58 (2008).

    Article  CAS  Google Scholar 

  23. Brew, H.M., Hallows, J.L. & Tempel, B.L. Hyperexcitability and reduced low threshold potassium currents in auditory neurons of mice lacking the channel subunit Kv1.1. J. Physiol. (Lond.) 548, 1–20 (2003).

    Article  CAS  Google Scholar 

  24. Sokolov, M.V., Shamotienko, O., Dhochartaigh, S.N., Sack, J.T. & Dolly, J.O. Concatemers of brain Kv1 channel alpha subunits that give similar K+ currents yield pharmacologically distinguishable heteromers. Neuropharmacology 53, 272–282 (2007).

    Article  CAS  Google Scholar 

  25. Sheng, M., Tsaur, M.L., Jan, Y.N. & Jan, L.Y. Contrasting subcellular localization of the Kv1.2 K+ channel subunit in different neurons of rat brain. J. Neurosci. 14, 2408–2417 (1994).

    Article  CAS  Google Scholar 

  26. Wang, H., Kunkel, D.D., Schwartzkroin, P.A. & Tempel, B.L. Localization of Kv1.1 and Kv1.2, two K channel proteins, to synaptic terminals, somata and dendrites in the mouse brain. J. Neurosci. 14, 4588–4599 (1994).

    Article  CAS  Google Scholar 

  27. Bekkers, J.M. & Delaney, A.J. Modulation of excitability by alpha-dendrotoxin–sensitive potassium channels in neocortical pyramidal neurons. J. Neurosci. 21, 6553–6560 (2001).

    Article  CAS  Google Scholar 

  28. Goldberg, E.M. et al. K+ channels at the axon initial segment dampen near-threshold excitability of neocortical fast-spiking GABAergic interneurons. Neuron 58, 387–400 (2008).

    Article  CAS  Google Scholar 

  29. Kole, M.H., Letzkus, J.J. & Stuart, G.J. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy. Neuron 55, 633–647 (2007).

    Article  CAS  Google Scholar 

  30. Shu, Y., Yu, Y., Yang, J. & McCormick, D.A. Selective control of cortical axonal spikes by a slowly inactivating K+ current. Proc. Natl. Acad. Sci. USA 104, 11453–11458 (2007).

    Article  CAS  Google Scholar 

  31. Mckay, B.E., Molineux, M.L., Mehaffey, W.H. & Turner, R.W. Kv1 K+ channels control Purkinje cell output to facilitate postsynaptic rebound discharge in deep cerebellar neurons. J. Neurosci. 25, 1481–1492 (2005).

    Article  CAS  Google Scholar 

  32. Metz, A.E., Spruston, N. & Martina, M. Dendritic D-type potassium currents inhibit the spike afterdepolarization in rat hippocampal CA1 pyramidal neurons. J. Physiol. (Lond.) 581, 175–187 (2007).

    Article  CAS  Google Scholar 

  33. Storm, J.F. Temporal integration by a slowly inactivating K+ current in hippocampal neurons. Nature 336, 379–381 (1988).

    Article  CAS  Google Scholar 

  34. Yamada, R. Hyperpolarization-activated cyclic nucleotide-gated cation channels regulate auditory coincidence detection in nucleus laminaris of the chick. J. Neurosci. 25, 8867–8877 (2005).

    Article  CAS  Google Scholar 

  35. Ashida, G., Abe, K., Funabiki, K. & Konishi, M. Passive soma facilitates submillisecond coincidence detection in the owl's auditory system. J. Neurophysiol. 97, 2267–2282 (2007).

    Article  Google Scholar 

  36. Barnes-Davies, M., Barker, M.C., Osmani, F. & Forsythe, I.D. Kv1 currents mediate a gradient of principal neuron excitability across the tonotopic axis in the rat lateral superior olive. Eur. J. Neurosci. 19, 325–333 (2004).

    Article  Google Scholar 

  37. Brew, H.M. & Forsythe, I.D. Two voltage-dependent K+ conductances with complementary functions in postsynaptic integration at a central auditory synapse. J. Neurosci. 15, 8011–8022 (1995).

    Article  CAS  Google Scholar 

  38. Oertel, D., Bal, R., Gardner, S.M., Smith, P.H. & Joris, P.X. Detection of synchrony in the activity of auditory nerve fibers by octopus cells of the mammalian cochlear nucleus. Proc. Natl. Acad. Sci. USA 97, 11773–11779 (2000).

    Article  CAS  Google Scholar 

  39. Reyes, A.D., Rubel, E.W. & Spain, W.J. Membrane properties underlying the firing of neurons in the avian cochlear nucleus. J. Neurosci. 14, 5352–5364 (1994).

    Article  CAS  Google Scholar 

  40. Rothman, J.S. & Manis, P.B. The roles potassium currents play in regulating the electrical activity of ventral cochlear nucleus neurons. J. Neurophysiol. 89, 3097–3113 (2003).

    Article  CAS  Google Scholar 

  41. Ferragamo, M.J. & Oertel, D. Octopus cells of the mammalian ventral cochlear nucleus sense the rate of depolarization. J. Neurophysiol. 87, 2262–2270 (2002).

    Article  Google Scholar 

  42. Rathouz, M. & Trussell, L. Characterization of outward currents in neurons of the avian nucleus magnocellularis. J. Neurophysiol. 80, 2824–2835 (1998).

    Article  CAS  Google Scholar 

  43. Svirskis, G., Kotak, V., Sanes, D.H. & Rinzel, J. Sodium along with low-threshold potassium currents enhance coincidence detection of subthreshold noisy signals in MSO neurons. J. Neurophysiol. 91, 2465–2473 (2004).

    Article  CAS  Google Scholar 

  44. McGinley, M.J. & Oertel, D. Rate thresholds determine the precision of temporal integration in principal cells of the ventral cochlear nucleus. Hear. Res. 216-217, 52–63 (2006).

    Article  Google Scholar 

  45. Jeffress, L.A. A place theory of sound localization. J. Comp. Physiol. Psychol. 41, 35–39 (1948).

    Article  CAS  Google Scholar 

  46. 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).

    Article  CAS  Google Scholar 

  47. McAlpine, D., Jiang, D. & Palmer, A.R. A neural code for low-frequency sound localization in mammals. Nat. Neurosci. 4, 396–401 (2001).

    Article  CAS  Google Scholar 

  48. Willms, A.R. NEUROFIT: software for fitting Hodgkin-Huxley models to voltage-clamp data. J. Neurosci. Methods 121, 139–150 (2002).

    Article  Google Scholar 

  49. Koch, C. & Segev, I. Methods in Neuronal Modeling: from Ions to Networks (MIT Press, Cambridge, Massachusetts, 1998).

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Acknowledgements

We thank D. Johnston and A. Reyes for their comments on a previous version of the manuscript. This work was supported by grants from the US National Institutes of Health (DC006877 to N.L.G. and DC008543 to J.R.) and Ruth Kirschstein National Research Service Awards to P.J.M and L.L.S.

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Author notes

  1. Paul J Mathews and Pablo E Jercog: These authors contributed equally to this work.

Authors and Affiliations

  1. Section of Neurobiology and Institute for Neuroscience, University of Texas at Austin, Austin, Texas, USA

    Paul J Mathews, Luisa L Scott & Nace L Golding

  2. Center for Neural Science, New York University, New York, New York, USA

    Pablo E Jercog & John Rinzel

  3. Courant Institute of Mathematical Sciences, New York University, New York, New York, USA

    John Rinzel

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  1. Paul J Mathews
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Contributions

P.J.M. performed all of the voltage-clamp experiments characterizing IK-LVA in patches and whole cells. N.L.G. conducted dual somatic and dendritic current-clamp recordings. L.L.S. performed some of the experiments from older animals and also made some of the initial observations on voltage-dependent sharpening. P.E.J. performed all of the simulations. N.L.G. and J.R. helped design and supervise the experiments and simulations, respectively. N.L.G. wrote the manuscript, with contributions from P.J.M., P.E.J. and J.R.

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Correspondence to Nace L Golding.

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Mathews, P., Jercog, P., Rinzel, J. et al. Control of submillisecond synaptic timing in binaural coincidence detectors by Kv1 channels. Nat Neurosci 13, 601–609 (2010). https://doi.org/10.1038/nn.2530

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