Minireview
Physiology, pharmacology and plasticity at the inner hair cell synaptic complex

https://doi.org/10.1016/j.heares.2006.08.017Get rights and content

Abstract

This report summarizes recent neuropharmacological data at the IHC afferent/efferent synaptic complex: the type of Glu receptors and transporter involved and the modulation of this fast synaptic transmission by the lateral efferents. Neuropharmacological data were obtained by coupling the recording of cochlear potentials and single unit of the auditory nerve with intra-cochlear applications of drugs (multi-barrel pipette). We also describe the IHC afferent/efferent functioning in pathological conditions. After acoustic trauma or ischemia, acute disruption of IHC-auditory dendrite synapses are seen. However, a re-growth of the nerve fibres and a re-afferentation of the IHC were completely done 5 days after injury. During this synaptic repair, multiple presynaptic bodies were commonly found, either linked to the membrane or “floating” in ectopic positions. In the meantime, the lateral efferents directly contact the IHCs. The demonstration that NMDA receptors blockade delayed the re-growth of neurites suggests a neurotrophic role of NMDA receptors in pathological conditions.

Section snippets

AMPA-preferring receptors mediate fast synaptic neurotransmission

Analysis of ionotropic glutamate (Glu) receptors with gene expression, immunocytochemistry and in situ hybridization indicates that spiral ganglion neurons expressed NMDA (NR1 and NR2A-D), AMPA (GluR2-4, see Fig. 1B), kainate (GluR5-7) receptor sub-units, as well as the high affinity kainate binding proteins (KA1 and KA2) (Pujol et al., 1985, Pujol et al., 1993, Gil-Loyzaga and Pujol, 1990, Puel, 1995). This suggests that NMDA, AMPA and kainate receptors might co-exist in ganglion neurons.

The Glu transporter Glast regulates fast synaptic transmission

Glutamate transporters form a powerful uptake system that rapidly eliminates glutamate from the extracellular spaces (Seal and Amara, 1999, Sims and Robinson, 1999, Tanaka, 2000, Danbolt, 2001). Five subtypes of Na+-dependent glutamate transporters have been cloned and identified to date, in various species, including humans: GLAST (excitatory amino acid transporter, EAAT1, glutamate aspartate transporter; Storck et al., 1992, Tanaka, 1993); GLT-1 (EAAT2, glutamate transporter; Pines et al.,

Modulation of the Glu synapse by the lateral olivocochlear efferents

Most of the data for lateral olivocochlear (LOC) efferents are based on lesioning studies of the entire olivocochlear bundle, including both LOC and MOC (medial olivo-cochlear) efferents. Only two studies have reported changes in auditory nerve response following complete cochlear de-efferentation in adult animals (Liberman, 1990, Zheng et al., 1999). The de-efferented ears showed very little change in threshold levels, but a very large decrease in the spontaneous discharge rate. Selective

Glutamate excitotoxicity and regeneration

To date, kainate, AMPA and glutamate have been reported to be neurotoxic in the cochlea in vivo. An acute exposure to these agonists results in a dose dependent swelling of radial dendrites (Pujol et al., 1985, Gil-Loyzaga and Pujol, 1990, Puel et al., 1991, Puel et al., 1994). Kainate, after a week survival time, also causes a loss of spiral ganglion neurons (Juiz et al., 1989, Janssen et al., 1991). There is a striking similarity of damage at the level of radial dendrites between acute

Conclusions

As already pointed out in describing electron microscopic findings, the mechanism of regeneration of auditory dendrites and neo-synaptogenesis after an excitotoxic injury seems to mimic normal development. Thus it would be important to investigate also for an involvement of neurotrophic factors and other molecules which are known to play a role in the growth and guidance of neurites. Another type of molecule could also play a more specific role: the lateral efferent neurotransmitters (see Fig. 1

References (74)

  • J.M. Juiz et al.

    The effects of kainic acid on the cochlear ganglion of the rat

    Hear. Res.

    (1989)
  • S. Ladrech et al.

    Microtubule-associated protein 2 (MAP2) expression during synaptic plasticity in the guinea pig cochlea

    Hear. Res.

    (2003)
  • H.-S. Li et al.

    Identification of a glutamate/aspartate transporter in the rat cochlea

    Hear. Res.

    (1994)
  • M.C. Liberman

    Effects of chronic cochlear de-efferentation on auditory-nerve response

    Hear. Res.

    (1990)
  • C.M. McMahon et al.

    Transient focal cooling at the round window and cochlear nucleus shows round window CAP originates from cochlear neurones alone

    Hear. Res.

    (2004)
  • W.H. Mulders et al.

    Catecholaminergic innervation of guinea pig superior olivary complex

    J. Chem. Neuroanat.

    (2005)
  • S. Namura et al.

    Inhibition of glial glutamate transporter GLT-1 augments brain edema after transient focal cerebral ischemia in mice

    Neurosci. Let.

    (2002)
  • E. Oestreicher et al.

    Dopamine regulates the glutamatergic inner hair cell activity in guinea pigs

    Hear. Res.

    (1997)
  • B.G. Peng et al.

    Aspirin selectively augmented N-methyl-d-aspartate types of glutamate responses in cultured spiral ganglion neurons of mice

    Neurosci. Lett.

    (2003)
  • J.-L. Puel

    Chemical synaptic transmission in the cochlea

    Prog. Neurobiol.

    (1995)
  • J.-L. Puel et al.

    α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) electrophysiological and neurotoxic effects in the guinea pig cochlea

    Neuroscience

    (1991)
  • R. Pujol et al.

    Kainic acid selectivity alters auditory dendrites connected with cochlear inner hair cells

    Hear. Res.

    (1985)
  • D. Robertson

    Functional significance of dendritic swelling after loud sounds in the guinea pig cochlea

    Hear. Res.

    (1983)
  • J. Ruel et al.

    The selective AMPA receptor antagonist GYKI 53784 blocks action potential generation and excitotoxicity in the guinea pig cochlea

    Neuropharmacology

    (2000)
  • K. Tanaka

    Cloning and expression of a glutamate transporter from mouse brain

    Neurosci. Lett.

    (1993)
  • K. Tanaka

    Functions of glutamate transporters in the brain

    Neurosci. Res.

    (2000)
  • J.L. Arriza et al.

    Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance

    Proc. Natl. Acad. Sci. USA

    (1997)
  • T.E. Billett et al.

    The nature and progression of injury in the organ of Corti during ischemia

    Hear. Res.

    (1989)
  • R. Bleakman et al.

    Pharmacological discrimination of GluR5 and GluR6 kainate receptor subtypes by (3S,4aR,6R,8aR)-6-[2-(1(2)H-tetrazole-5-yl)ethyl]decahydroisdoquinoline-3 carboxylic-acid

    Mol. Pharmacol.

    (1996)
  • M. Eybalin

    Neurotransmitters and neuromodulators of the mammalian cochlea

    Physiol. Rev.

    (1993)
  • W.A. Fairman et al.

    An excitatory amino-acid transporter with properties of a ligand-gated chloride channel

    Nature

    (1995)
  • D. Felix et al.

    A microiontophoretic study of the role of excitatory amino acids at the afferent synapses of mammalian inner hair cells

    Eur. Arch. Otorhinolaryngol.

    (1990)
  • D.N. Furness et al.

    Immunocytochemical localization of a high-affinity glutamate-aspartate transporter, GLAST, in rat and guinea-pig cochlea

    Eur. J. Neurosci.

    (1997)
  • P. Gil-Loyzaga et al.

    Neurotoxicity of kainic acid in the rat cochlea during early developmental stages

    Eur. Arch. Oto-Rhino-Laryngol.

    (1990)
  • E. Glowatzki et al.

    Transmitter release at the hair cell ribbon synapse

    Nat. Neurosci.

    (2002)
  • J.A. Groff et al.

    Modulation of cochlear afferent response by the lateral olivocochlear system: activation via electrical stimulation of the inferior colliculus

    J. Neurophysiol.

    (2003)
  • I.M. Hunter-Duvar

    Morphology of the normal and acoustically damaged cochlea

    Scan. Electron Microsc.

    (1977)
  • Cited by (147)

    • Excitotoxic damage to auditory nerve afferents and spiral ganglion neurons is correlated with developmental upregulation of AMPA and KA receptors

      2021, Hearing Research
      Citation Excerpt :

      Glutamate is recognized at the neurotransmitter released by IHCs on to the peripheral type I afferent terminals of SGNs. AMPA, kainate and NMDA receptors are expressed on type I auditory nerve fibers and SGNs (Puel, 1995; Ruel et al., 2007). The release and reuptake of glutamate from IHCs and the number of GluRs expressed on the afferent nerve terminal is tightly regulated to optimize fast synaptic transmission and maintain homeostatic conditions (Chen et al., 2009; Furness and Lehre, 1997; Peppi et al., 2012; Puel et al., 2002b).

    View all citing articles on Scopus
    View full text