Elsevier

Neuroscience

Volume 154, Issue 1, 12 June 2008, Pages 77-86
Neuroscience

Cochlear nucleus
In the ventral cochlear nucleus Kv1.1 and subunits of HCN1 are colocalized at surfaces of neurons that have low-voltage-activated and hyperpolarization-activated conductances

https://doi.org/10.1016/j.neuroscience.2008.01.085Get rights and content

Abstract

Principal cells of the ventral cochlear nucleus (VCN) differ in the magnitudes of low-voltage-activated potassium (gKL) and hyperpolarization-activated (gh) conductances that determine the time course of signaling. Octopus cells in mice have large gKL (500 nS) and gh (150 nS), bushy cells have smaller gKL (80 nS) and gh (30 nS), and T stellate cells have little gKL and a small gh (20 nS). gKL Arises through potassium channels of which ∼60% contain Kv1.1 (potassium channels in the shaker or KCNA family) subunits; gh arises through channels that include hyperpolarization and cyclic nucleotide gated (HCN) 1 subunits. The surfaces of cell bodies and dendrites of octopus cells in the dorsocaudal pole, and of similar cells along the ventrolateral edge of the PVCN, were brightly labeled by an antibody against HCN1 that was colocalized with labeling for Kv1.1. More anteriorly neurons with little surface labeling were intermingled among cell bodies and dendrites with surface labeling for both proteins, likely corresponding to T stellate and bushy cells. The membrane-associated labeling patterns for Kv1.1 and HCN1 were consistent with what is known about the distribution and the electrophysiological properties of the principal cells of the VCN. The cytoplasm of large cells and axonal paranodes contained immunofluorescent labeling for only Kv1.1.

Section snippets

Mice

Mice of the outbred ICR strain and obtained from Sprague–Dawley (Madison, WI, USA) were used in these studies. All animal protocols were approved by the Institutional Animal Care and Use Committee of the School of Medicine and Public Health at the University of Wisconsin, Madison and conform with the guidelines established by the National Institutes of Health in the USA, Care and Use of Laboratory Animals (NIH publications No. 80-23. Care was taken to use as few mice as possible and to cause

Electrophysiology

Whole-cell patch-clamp recordings in the voltage-clamp mode reveal the properties of the ion channels that mediate IKL and Ih. Examples of such recordings are illustrated in Fig. 1. In all recordings some currents were blocked pharmacologically: 0.25 mM Cd2+ blocked voltage-gated Ca2+ currents, 1 μM TTX blocked voltage-gated Na+ currents, 40 μM DNQX blocked spontaneous EPSCs through AMPA receptors, and 1 μM strychnine blocked spontaneous IPSCs through glycine receptors. The upper panels

Discussion

There was a strong correlation between electrophysiological measurements of voltage-sensitive conductances and surface labeling for subunits of ion channels that mediate those conductances. The octopus cells that have exceptionally strong gKL and gh have surfaces that are the most brightly labeled for HCN1 that is colocalized with Kv1.1 at the surfaces of cell bodies and dendrites. An unexpected finding was that cells whose labeling for these antigens resembles that of octopus cells were found

Conclusion

In summary, the present study leads to the following conclusions. 1) Surface labeling for Kv1.1 and HCN1 is correlated with the magnitude of maximal gKL and gh measured in neurons in those areas. Surface labeling is strong for octopus cells, and for a population of cells that is sparsely distributed over the VCN that might correspond to D stellate cells, less strong for bushy cells, and least for T stellate cells. 2) In octopus cells, and probably also bushy cells, gKL and gh are likely to be

Acknowledgments

We are most grateful to Ed Chapman for giving us the opportunity to use the confocal microscope and to Camin Dean and Felix Yeh who answered our questions patiently and graciously. Two anonymous reviewers pointed out several significant shortcomings and omissions in a very nice way; thank you! We thank Samantha Wright for her valuable comments. We also thank Ravi Kochhar and the departmental office staff for their continuing support. This work was supported by a grant from NIH DC 00176.

References (53)

  • R. Bal et al.

    Hyperpolarization-activated, mixed-cation current (Ih) in octopus cells of the mammalian cochlear nucleus

    J Neurophysiol

    (2000)
  • R. Bal et al.

    Potassium currents in octopus cells of the mammalian cochlear nuclei

    J Neurophysiol

    (2001)
  • M. Barnes-Davies et al.

    Kv1 currents mediate a gradient of principal neuron excitability across the tonotopic axis in the rat lateral superior olive

    Eur J Neurosci

    (2004)
  • H.M. Brew et al.

    Hyperexcitability and reduced low threshold potassium currents in auditory neurons of mice lacking the channel subunit Kv1.1

    J Physiol (Lond)

    (2003)
  • X. Cao et al.

    Temperature affects voltage-sensitive conductances differentially in octopus cells of the mammalian cochlear nucleus

    J Neurophysiol

    (2005)
  • X.J. Cao et al.

    Voltage-sensitive conductances of bushy cells of the mammalian ventral cochlear nucleus

    J Neurophysiol

    (2007)
  • S. Chen et al.

    Properties of hyperpolarization-activated pacemaker current defined by coassembly of HCN1 and HCN2 subunits and basal modulation by cyclic nucleotide

    J Gen Physiol

    (2001)
  • P.D. Dodson et al.

    Presynaptic rat Kv1.2 channels suppress synaptic terminal hyperexcitability following action potential invasion

    J Physiol

    (2003)
  • J.R. Doucet et al.

    Projections from the ventral cochlear nucleus to the dorsal cochlear nucleus in rats

    J Comp Neurol

    (1997)
  • M.J. Ferragamo et al.

    Octopus cells of the mammalian ventral cochlear nucleus sense the rate of depolarization

    J Neurophysiol

    (2002)
  • K. Fujino et al.

    Cholinergic modulation of stellate cells in the mammalian ventral cochlear nucleus

    J Neurosci

    (2001)
  • I. Fukui et al.

    Tonotopic gradients of membrane and synaptic properties for neurons of the chicken nucleus magnocellularis

    J Neurosci

    (2004)
  • N.L. Golding et al.

    Physiological identification of the targets of cartwheel cells in the dorsal cochlear nucleus

    J Neurophysiol

    (1997)
  • N.L. Golding et al.

    Recordings from slices indicate that octopus cells of the cochlear nucleus detect coincident firing of auditory nerve fibers with temporal precision

    J Neurosci

    (1995)
  • U. Koch et al.

    Distribution of HCN1 and HCN2 in rat auditory brainstem nuclei

    Eur J Neurosci

    (2004)
  • H. Kuba et al.

    Tonotopic specialization of auditory coincidence detection in nucleus laminaris of the chick

    J Neurosci

    (2005)
  • Cited by (44)

    • 2.35 - Coding of Temporal Information

      2020, The Senses: A Comprehensive Reference: Volume 1-7, Second Edition
    • The ion channels and synapses responsible for the physiological diversity of mammalian lower brainstem auditory neurons

      2019, Hearing Research
      Citation Excerpt :

      The low membrane resistance creates a fast membrane time constant that favors the speed and precision of firing, and impairs the integration of synaptic potentials, resulting in a single post-synaptic action potential per presynaptic action potential (Oertel, 1983; Smith and Rhode, 1987). The presence of a prominent hyperpolarization activated cationic current (Ih) produced by the expression of the subunits HCN1 and HCN4 is the main contributor for the low membrane resistance of bushy cells (Schwarz and Puil, 1997; Leao et al., 2006; Cao et al., 2007; Oertel et al., 2008). Additionally, a reduced expression of voltage-dependent sodium conductances in the soma of bushy cells enhances precision and fidelity of action potential firing in these neurons (Yang et al., 2016).

    • Genetic perturbations suggest a role of the resting potential in regulating the expression of the ion channels of the KCNA and HCN families in octopus cells of the ventral cochlear nucleus

      2017, Hearing Research
      Citation Excerpt :

      The HCN channels that mediate Ih are permeable to both Na+ and K+ and have a reversal potential of −40 mV so that Ih is inward at the resting potential in octopus and many other types of neurons (Banks et al., 1993; Bal and Oertel, 2000). HCN1 and Kv1.1 are colocalized in the somatic and dendritic octopus cell membrane (Oertel et al., 2008; Rusznak et al., 2008; Robbins and Tempel, 2012). In an earlier study we examined mice in which HCN1 was eliminated to alter gh (Cao and Oertel, 2011).

    • A mechanistic understanding of the role of feedforward inhibition in the mammalian sound localization circuitry

      2013, Neuron
      Citation Excerpt :

      Thus, the interplay between inhibition and Kv1 channels provides a mechanism that helps preserve the timing of EPSPs while simultaneously sharpening binaural coincidence detection. Kv1-containing K+ channels are broadly expressed in many areas of the brain (Sheng et al., 1994; Wang et al., 1994; Trimmer and Rhodes, 2004) and are found in especially high density in auditory brainstem neurons concerned with the precise coding of temporal information, including the MSO (e.g., Bal and Oertel, 2001; Dodson et al., 2002; Rothman and Manis, 2003; Oertel et al., 2008; Johnston et al., 2010). Mouse knockouts of Kv1.1 show deficits in sound localization (Allen and Ison, 2012), probably reflecting altered excitability and precision in neurons of the superior olivary nuclei and their associated inputs (Brew et al., 2003; Kopp-Scheinpflug et al., 2003; Gittelman and Tempel, 2006).

    View all citing articles on Scopus
    View full text