Loss of GABAB receptors in cochlear neurons: threshold elevation suggests modulation of outer hair cell function by type II afferent fibers

J Assoc Res Otolaryngol. 2009 Mar;10(1):50-63. doi: 10.1007/s10162-008-0138-7. Epub 2008 Oct 17.

Abstract

Despite pharmacological and immunohistochemical evidence for GABA as a neurotransmitter in the olivocochlear efferent bundle, a clear functional role of GABA in the inner ear has not emerged. To explore the role of metabotropic GABA(B) receptors, we characterized the cochlear phenotype of mice with targeted deletion of the GABA(B1) subunit and determined its tissue localization using a mouse line expressing a GFP-tagged GABA(B1) subunit under the endogenous promoter. Immunostaining revealed GABA(B1) expression in both type I and type II ganglion cells and in their synaptic terminals under inner and outer hair cells, respectively. No GABA(B1) expression was observed in hair cells. Mean cochlear thresholds, measured via both auditory brainstem responses and distortion product otoacoustic emissions (DPOAEs), were elevated by approximately 10 dB in GABA(B1)-deficient mice, consistent with outer hair cell dysfunction. Olivocochlear efferent function, assessed via DPOAE suppression during efferent electrical stimulation, was unaffected by GABA(B1) deletion. GABA(B1)-deficient mice showed increased resistance to permanent acoustic injury, with mean threshold shifts approximately 25 dB smaller than wild-types after exposure to 8-16-kHz noise at 100 dB for 2 h. In contrast, there was no vulnerability difference to temporary acoustic injury following exposure to the same noise at 94 dB for 15 min. Our results suggest that GABAergic signaling in type II afferent neurons may be required for normal outer hair cell amplifier function at low sound levels and may also modulate outer hair cell responses to high-level sound.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Auditory Threshold / physiology*
  • Cholinergic Antagonists / pharmacology
  • Cochlear Nerve / metabolism*
  • Glycine Agents / pharmacology
  • Green Fluorescent Proteins
  • Hair Cells, Auditory, Inner / physiology
  • Hair Cells, Auditory, Outer / physiology*
  • Hearing Loss, Noise-Induced
  • Mice
  • Mice, Knockout
  • Neurons, Afferent / physiology*
  • Neurons, Efferent / physiology
  • Presynaptic Terminals / metabolism
  • Receptors, GABA-B / deficiency*
  • Recombinant Fusion Proteins
  • Strychnine / pharmacology

Substances

  • Cholinergic Antagonists
  • Glycine Agents
  • Receptors, GABA-B
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Strychnine