title: Altered vesicular glutamate transporter distributions in the mouse cochlear nucleus following cochlear insult.
abstract: Vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) have distinct distributions in the cochlear nucleus that correspond to sources of the labeled terminals. VGLUT1 is mainly associated with terminals of auditory nerve fibers, whereas VGLUT2 is mainly associated with glutamatergic terminals deriving from other sources that project to the cochlear nucleus (CN), including somatosensory and vestibular terminals. Previous studies in guinea pig have shown that cochlear damage results in a decrease of VGLUT1-labeled puncta and an increase in VGLUT2-labeled puncta. This indicates cross-modal compensation that is of potential importance in somatic tinnitus. To examine whether this effect is consistent across species and to provide a background for future studies, using transgenesis, the current study examines VGLUT expression profiles upon cochlear insult by intracochlear kanamycin injections in the mouse. Intracochlear kanamycin injections abolished ipsilateral ABR responses in all animals and reduced ipsilateral spiral ganglion neuron densities in animals that were sacrificed after four weeks, but not in animals that were sacrificed after three weeks. In all unilaterally deafened animals, VGLUT1 density was decreased in CN regions that receive auditory nerve fiber terminals, i.e., in the deep layer of the dorsal cochlear nucleus (DCN), in the interstitial region where the auditory nerve enters the CN, and in the magnocellular region of the antero- and posteroventral CN. In contrast, density of VGLUT2 expression was upregulated in the fusiform cell layer of the DCN and in the granule cell lamina, which are known to receive somatosensory and vestibular terminals. These results show that a cochlear insult induces cross-modal compensation in the cochlear nucleus of the mouse, confirming previous findings in guinea pig, and that these changes are not dependent on the occurrence of spiral ganglion neuron degeneration.
authors.affiliation: Kresge Hearing Research Institute, Otolaryngology, University of Michigan, United States.
authors.forename: A N
authors.initials: AN
authors.lastname: Heeringa
authors.affiliation: Kresge Hearing Research Institute, Otolaryngology, University of Michigan, United States.
authors.forename: R A
authors.initials: RA
authors.lastname: Stefanescu
authors.affiliation: Kresge Hearing Research Institute, Otolaryngology, University of Michigan, United States.
authors.forename: Y
authors.initials: Y
authors.lastname: Raphael
authors.affiliation: Kresge Hearing Research Institute, Otolaryngology, University of Michigan, United States; Molecular and Integrative Physiology, University of Michigan, United States; Biomedical Engineering, University of Michigan, United States. Electronic address: sushore@umich.edu.
authors.forename: S E
authors.initials: SE
authors.lastname: Shore
mesh_terms: D000818:Animals; D002452:Cell Count; D015834:Cochlear Diseases / Q000473:pathology / Q000503:physiopathology*; D017626:Cochlear Nucleus / Q000473:pathology / Q000503:physiopathology*; D003638:Deafness / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D007839:Functional Laterality; D007150:Immunohistochemistry; D007612:Kanamycin; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D013136:Spiral Ganglion / Q000378:metabolism / Q000473:pathology; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism*
chemical_list: C493477:Slc17a6 protein, mouse; C493465:Slc17a7 protein, mouse; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D007612:Kanamycin
keywords: cochlear damage; cochlear nucleus; multisensory; plasticity; tinnitus; vesicular glutamate transporters