title: Dopamine in the auditory brainstem and midbrain: co-localization with amino acid neurotransmitters and gene expression following cochlear trauma.
abstract: Dopamine (DA) modulates the effects of amino acid neurotransmitters (AANs), including GABA and glutamate, in motor, visual, olfactory, and reward systems (Hnasko et al., 2010; Stuber et al., 2010; Hnasko and Edwards, 2012). The results suggest that DA may play a similar modulatory role in the auditory pathways. Previous studies have shown that deafness results in decreased GABA release, changes in excitatory neurotransmitter levels, and increased spontaneous neuronal activity within brainstem regions related to auditory function. Modulation of the expression and localization of tyrosine hydroxylase (TH; the rate limiting enzyme in the production of DA) in the IC following cochlear trauma has been previously reported (Tong et al., 2005). In the current study the possibility of co-localization of TH with AANs was examined. Changes in the gene expression of TH were compared with changes in the gene expression of markers for AANs in the cochlear nucleus (CN) and inferior colliculus (IC) to determine whether those deafness related changes occur concurrently. The results indicate that bilateral cochlear ablation significantly reduced TH gene expression in the CN after 2 months while in the IC the reduction in TH was observed at both 3 days and 2 months following ablation. Furthermore, in the CN, glycine transporter 2 (GLYT2) and the GABA transporter (GABAtp) were also significantly reduced only after 2 months. However, in the IC, DA receptor 1 (DRDA1), vesicular glutamate transporters 2 and 3 (VGLUT2, VGLUT3), GABAtp and GAD67 were reduced in expression both at the 3 days and 2 months time points. A close relationship between the distribution of TH and several of the AANs was determined in both the CN and the IC. In addition, GLYT2 and VGLUT3 each co-localized with TH within IC somata and dendrites. Therefore, the results of the current study suggest that DA is spatially well positioned to influence the effects of AANs on auditory neurons.
authors.affiliation: Molecular Anatomy of Auditory-related Central Systems, Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit MI, USA.
authors.forename: Bozena E
authors.initials: BE
authors.lastname: Fyk-Kolodziej
authors.affiliation: Department of Otolaryngology, Kansai Medical University Osaka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimano
authors.affiliation: Molecular Anatomy of Auditory-related Central Systems, Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit MI, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Gafoor
authors.affiliation: Molecular Anatomy of Auditory-related Central Systems, Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit MI, USA.
authors.forename: Najab
authors.initials: N
authors.lastname: Mirza
authors.affiliation: Molecular Anatomy of Auditory-related Central Systems, Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit MI, USA.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Griffith
authors.affiliation: Kresge Hearing Research Institute, University of Michigan School of Medicine, Ann Arbor MI, USA.
authors.forename: Tzy-Wen
authors.initials: TW
authors.lastname: Gong
authors.affiliation: Molecular Anatomy of Auditory-related Central Systems, Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit MI, USA.
authors.forename: Avril Genene
authors.initials: AG
authors.lastname: Holt
keywords: Sprague–Dawley rat; cochlear ablation; cochlear nucleus; hearing loss; immunocytochemistry; inferior colliculus; real time PCR; tyrosine hydroxylase