Elsevier

Hearing Research

Volume 267, Issues 1–2, 1 August 2010, Pages 12-26
Hearing Research

Research paper
Evidence that the compound action potential (CAP) from the auditory nerve is a stationary potential generated across dura mater

https://doi.org/10.1016/j.heares.2010.03.091Get rights and content

Abstract

We have investigated the generation of the compound action potential (CAP) from the auditory nerve of guinea pigs. Responses to acoustic tone-bursts were recorded from the round window (RW), throughout the cochlear fluids, from the surface of the cochlear nucleus, from the central end of the auditory nerve after removal of the cochlear nucleus, from the scalp vertex, and from the contralateral ear. Responses were compared before, during and after experimental manipulations including pharmacological blockade of the auditory nerve, section of the auditory nerve, section of the efferent nerves, removal of the cochlear nucleus, and focal cooling of the cochlear nerve and/or cochlear nucleus. Regardless of the waveform changes occurring with these manipulations, the responses were similar in waveform but inverted polarity across the internal auditory meatus. The CAP waveforms were very similar before and after removal of the cochlear nucleus, apart from transient changes that could last many minutes. This suggests that the main CAP components are generated entirely by the eighth nerve. Based on previous studies and a clear understanding of the generation of extracellular potentials, we suggest that the early components in the responses recorded from the round window, from the cochlear fluids, from the surface of the cochlear nucleus, or from the scalp are a far-field or stationary potential, generated when the circulating action currents associated with each auditory neurone encounters a high extracellular resistance as it passes through the dura mater.

Introduction

The compound action potential (CAP) from the auditory nerve is measured clinically in humans, either trans-tympanically on the round window or boney prominence, or more recently from the surface of the tympanum (Ferraro and Durrant, 2002, Noguchi et al., 1999, Brown, 2007). In this study we have investigated the generation of this response in guinea pigs, monitoring the CAP at the round window, within the cochlea, within the braincase or at the surface of the scalp, while disrupting auditory nerve function with either direct mechanical pressure or chilling of the auditory nerve as it exits the internal auditory meatus and travels to the brainstem.

During the 1970s clinicians began to use changes in the CAP as a diagnostic measure of several cochlear nerve pathologies, such as vestibular schwannoma or Meniere’s disease (Beagley and Gibson, 1976, Gibson and Beagley, 1976), but such electrocochleography (ECochG) became progressively less popular, partly due to improvements in MRI and OAE, partly due to the invasiveness and variability of the ECochG technique, and partly due to the lack of a clear understanding of the link between the changes in the CAP and the underlying pathologies. Currently ECochG is mainly used for detailed objective paediatric assessment, by some in the diagnosis of Ménière’s disease (where the ratio of CAP to summating potential or SP amplitude is considered important), and in monitoring peripheral hearing function during cochlear nerve surgery.

Unfortunately there is still a poor understanding of how the CAP is generated, and what any changes in CAP waveshape might indicate about cochlear or auditory nerve function (Ferraro and Durrant, 2002), although in 1958 Goldstein and Kiang (1958) described the CAP waveform as the weighted, summated extracellular response generated by individual neurones firing synchronously at the onset of an acoustic stimulus. The single neurone contribution to the extracellular electrical population response (the compound action potential or CAP) as it fires once is referred to here as the unitary potential (UP; referred to earlier by Kiang et al. as the N0 response), and has been estimated in a number of studies by either (a) back-averaging the extracellular electrical activity triggered by spikes from single VIIIth nerve neurones (Kiang et al., 1976, Wang, 1979, Versnel et al., 1992), (b) theoretically, using the frequency characteristics of the CAP and the ensemble neural noise (de Boer, 1975, McMahon and Patuzzi, 2002), or (c) by measuring the CAP with and without acoustic masking the CAP with filtered noise, and then estimating single fibre contributions with progressive subtraction (Elberling, 1976). Apart from their amplitude, the UP and CAP obtained in those experiments were similar in waveshape, with the CAP measured at the round window (RW) resembling a damped 1 kHz sinusoid (Fig. 1), consisting of a series of three to four interleaved negative and positive peaks, here termed N1rw, P1rw, N2rw and P2rw, and so on. The analogous peaks in the response measured within the braincase (and near the CN when it is intact) are here termed P1cn, N1cn, P2cn, N2cn, and so on.

Even though the CAP waveform appears to be a weighted version of the UP waveform, there is still no clear understanding of how the UP is itself generated. It might be generated by ‘local’ near-field action currents (like the CAP recorded from the surface of a long nerve bundle), and/or a far-field potential (similar to the auditory brainstem response or ABR, recorded from the scalp). If the RW CAP consists of auditory nerve activity within the cochlea, then it could be used clinically to indicate abnormal peripheral generation of action potentials. On the other hand, if it contains components generated in the brainstem, it might provide a tool for diagnosing central pathologies or failed transmission between the cochlea and the brainstem.

To date, there have been three main views on the origins of the CAP. First, early studies suggested that the CAP recorded at the round window (RW) was generated at the internal auditory meatus (IAM), because the IAM is an electrical partition representing ‘a physiological electrode’ (Tasaki et al., 1954, Legouix and Pierson, 1974, Elberling, 1976, Teas et al., 1962). This early phrase ‘physiological electrode’ was used in the sense of a ‘sucrose gap electrode’ (Huxley and Stampfli, 1951, Stämpfli, 1954, Stys and Kocsis, 1995) commonly used to study neurones before the development of glass microelectrodes1. Both Tasaki et al. (1954) and Legouix and Pierson (1974) suggested that the CAP also included components generated near the recording electrode (near-field components), which were responsible for the differences in amplitude of the positive peaks in different cochlear turns.

Second, observations during surgery have suggested that the P1rw and N2rw peaks might be generated in the brainstem (Daigneault, 1974, Møller, 1983; Møller, 2000, Sellick et al., 2003). This view was primarily based on the observation that when the cochlear nucleus (CN) was removed, or the central end of the cochlear nerve was sectioned, the P1rw peak was abolished and the N1rw and N2rw peaks appeared to merge to produce one broad negative peak (Møller, 1983, McMahon and Patuzzi, 2002, Sellick et al., 2003). Furthermore, the response evoked by a high-frequency tone-burst measured at the surface of the CN also included a negative peak (N1cn) and a positive peak (P2cn) that followed the intial P1cn peak, and had absolute latencies similar to the positive P1rw and negative N2rw peaks in the CAP waveform.

Third, it has been suggested that the CAP contained some local components produced by action currents generated at the peripheral ends of the primary afferent neurones (McMahon et al., 2004, Brown et al., 2004). Specifically, it was suggested the N1rw peak was generated by Na+ influx, and the P1rw peak might be generated by K+ efflux from primary afferent cochlear nerves. This was supported by previous studies where the application of voltage-gated K+ channel blockers to the cochlear nerve abolished the P1rw peak (van Emst et al., 1996), and by micropipette recordings from beneath the myelin sheath of VIIIth nerve neurones (Robertson, 1975) where the K+ channels are localized (Chiu and Ritchie, 1981), which consisted of positive peaks similar to the P1rw peak in the CAP (Eng et al., 1988).

Our observations are consistent with the view that the CAP is almost completely a far-field potential (or a stationary potential2), generated by the circulating neural action currents (Fig. 1). The main negative (N1rw) and positive (P1rw) peaks at the round window are generated, respectively, when the leading and trailing travelling dipoles of these action currents encounter a change in the electrical resistance of the extracellular media as the action potential is conducted through the IAM and dura mater sheath towards the brainstem, while similar inverted peaks (P1cn and N1cn) are simultaneously generated within the braincase by these same two dipoles. Experimentally blocking or altering the propagation of these dipoles along the nerve would alter the response waveform depending on the particular manipulation.

Section snippets

Animal preparation

Experiments were performed on 24 normal adult guinea pigs (Cavia porcellus), with body weights between 300 and 450 g, and normal CAP thresholds. Animal preparation, anaesthesia and surgical protocols were sanctioned by the Animal Ethics Committee of The University of Western Australia. Anaesthesia commenced with a subcutaneous premedication of 0.1 mL of atrosine (0.6 mg/mL atropine sulphate; Apex Laboratories, N S W, Australia), and a 30 mg/kg body weight intraperitoneal injection of Nembutal

Characteristics of the normal CAP

The RW CAP waveform evoked by high-frequency tone-bursts consisted of a series of interleaved negative and positive peaks (conventionally termed N1, P1, N2, P2 and N3), riding on the summating potential (SP; Fig. 2A), and here referred to as N1rw, P1rw, N2rw, P2rw and N3rw. In the present study, the amplitudes of these peaks were defined from their initial point of inflection to the maximum or minimum of each peak or trough. The onset of the N1rw peak began less than 1 ms after the tone-burst

Discussion

This study has found that while the CAP waveshape at the cochlea changed with stimulus frequency, it was very similar throughout the cochlea and on the round window, suggesting that there was little or no near-field component in the responses. The ratio of its main response peaks (N1rw and P1rw) were maintained across stimulus level, apart from small changes as the early N1rw rode upon the SP response from hair cells. There were also small response components (edge-CAPs) produced inadvertently

References (56)

  • B.R. Schofield et al.

    Auditory cortical projections to the cochlear nucleus in guinea pigs

    Hear. Res.

    (2005)
  • P. Sellick et al.

    Primary afferent and cochlear nucleus contributions to extracellular potentials during tone-bursts

    Hear. Res.

    (2003)
  • H. Versnel et al.

    Single-fibre and whole nerve responses to clicks as a function of sound intensity in the guinea pig

    Hear. Res.

    (1992)
  • J.J. Zappia et al.

    Intraoperative auditory monitoring in acoustic neuroma surgery

    Otolaryngol. Head. Neck. Surg.

    (1996)
  • H.A. Beagley et al.

    Lesions mimicking acoustic neuromata on electrocochleography

  • D.E. Brackmann et al.

    Electrocochleography in Meniere’s disease and acoustic neuromas

  • Brown, D.J., 2007. Origins and use of the stochastic and sound-evoked extracellular electrical activity of the auditory...
  • E. de Boer

    Synthetic whole-nerve action potentials for the cat

    J. Acoust. Soc. Am.

    (1975)
  • M.E. Chertoff

    Analytic treatment of the compound action potential: estimating the summed post-stimulus time histogram and unit response

    J. Acoust. Soc. Am.

    (2004)
  • S.Y. Chiu et al.

    Evidence for the presence of potassium channels in the paranodal region of acutely demyelinated mammalian single nerve fibres

    J. Physiol.

    (1981)
  • A.R. Cody et al.

    Electrophysiological and morphological changes in the guinea pig cochlea following mechanical trauma to the organ of Corti

    Acta. Otolaryngol.

    (1980)
  • E.A. Daigneault

    Source of the P1 component of the cochlea round window recording

    Acta Otolaryngol.

    (1974)
  • P. Dallos

    The Auditory Periphery

    (1973)
  • J.J. Eggermont et al.

    Action potentials and summating potentials in the normal human cochlea

    Acta. Otolaryngol. Suppl.

    (1974)
  • C. Elberling

    Simulation of cochlear action potentials recorded from the ear canal in man

  • D.L. Eng et al.

    Development of 4-AP and TEA sensitivities in mammalian myelinated nerve fibers

    J. Neurophysiol.

    (1988)
  • J.A. Ferraro et al.

    Electrocochleography

  • H.M. Fishman et al.

    Vesicle-mediated restoration of a plasmalemmal barrier in severed axons

    News. Physiol. Sci.

    (2003)
  • Cited by (0)

    View full text