Localization of efferent neurotransmitters in the inner ear of the homozygous Bronx waltzer mutant mouse

Hear Res. 2002 May;167(1-2):136-55. doi: 10.1016/s0378-5955(02)00382-9.

Abstract

Naturally occurring mutant mice provide an excellent model for the study of genetic malformations of the inner ear. Mice homozygous for the Bronx waltzer (bv/bv) mutation are severely hearing impaired or deaf and exhibit a 'waltzing' gait. Functional aspects of cochlear and vestibular efferents in the bv/bv mutant mouse are not well known. The present study was designed to evaluate several candidates of efferent neurotransmitters or neuromodulators including choline acetyltransferase (ChAT), gamma-aminobutyric acid (GABA), and calcitonin gene-related peptide (CGRP) in the inner ear of the bv/bv mutant mouse. Ultrastructural investigations at both light and electron microscopic level were performed. Ultrastructural morphologic evaluations of the cochlea and the vestibular end-organs were also undertaken. It is demonstrated that ChAT, GABA and CGRP immunoreactivities are present in the cochlea and in vestibular end-organs of bv/bv mutant mice. In the organ of Corti, immunoreactivity of ChAT, GABA and CGRP is confined to the inner spiral fibers, tunnel-crossing fibers, and the vesiculated nerve endings synapsing with outer hair cells. Interestingly, immunoreactivity was detectable even where inner hair cells appeared missing. Results also revealed malformations of the outer hair cells with synaptic contacts to efferent nerve endings consistently intact. In the neurosensory epithelia of the vestibular end-organs, the presence of ChAT, GABA, and CGRP immunoreactivity was localized at the vestibular efferents, with the exception of the macula of saccule. In one 8-month-old macula of utricle where the depletion of hair cells appeared highest, ChAT immunostaining was still discernible. Ultrastructural investigation demonstrated that vesiculated efferent nerve endings make synaptic contact with the outer hair cells in the organ of Corti and with type II hair cells in the vestibular end-organs. The present study provides further support that the efferent system in the bv/bv mutant inner ear is morphologically as well as functionally mature. These findings also demonstrate that if and when the onset of efferent degeneration in the bv/bv mutant inner ear occurs, it transpires subsequent to pathological conditions in the hair cells. The present findings give further indication that the efferent systems of the bv/bv mutant inner ear are independent of the afferent systems in many aspects including development, maturation as well as degeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Auditory Pathways / metabolism
  • Calcitonin Gene-Related Peptide / metabolism
  • Choline O-Acetyltransferase / metabolism
  • Cochlea / metabolism
  • Cochlea / ultrastructure
  • Ear, Inner / abnormalities*
  • Ear, Inner / metabolism*
  • Ear, Inner / ultrastructure
  • Efferent Pathways / metabolism
  • Female
  • Hair Cells, Auditory, Inner / abnormalities
  • Hair Cells, Auditory, Inner / metabolism
  • Hair Cells, Auditory, Inner / ultrastructure
  • Hair Cells, Auditory, Outer / abnormalities
  • Hair Cells, Auditory, Outer / metabolism
  • Hair Cells, Auditory, Outer / ultrastructure
  • Immunohistochemistry
  • Male
  • Mice
  • Mice, Inbred CBA
  • Mice, Mutant Strains
  • Microscopy, Electron
  • Neurotransmitter Agents / metabolism*
  • Vestibule, Labyrinth / abnormalities
  • Vestibule, Labyrinth / metabolism
  • Vestibule, Labyrinth / ultrastructure
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Neurotransmitter Agents
  • gamma-Aminobutyric Acid
  • Choline O-Acetyltransferase
  • Calcitonin Gene-Related Peptide