Dopaminergic Signaling in the Cochlea: Receptor Expression Patterns and Deletion Phenotypes

Abstract

Pharmacological studies suggest that dopamine release from lateral olivocochlear efferent neurons suppresses spontaneous and sound-evoked activity in cochlear nerve fibers and helps control noise-induced excitotoxicity; however, the literature on cochlear expression and localization of dopamine receptors is contradictory. To better characterize cochlear dopaminergic signaling, we studied receptor localization using immunohistochemistry or RT-PCR and assessed histopathology, cochlear responses and olivocochlear function in mice with targeted deletion of each of the five receptor subtypes. In normal ears, D1, D2 and D5 receptors were detected in microdissected immature (P10–P13) spiral ganglion cells and outer hair cells but not inner hair cells. D4 was detected in spiral ganglion cells only. In whole cochlea samples from adults, transcripts for D1, D2, D4 and D5 were present, whereas D3 mRNA was never detected. D1 and D2 immunolabeling was localized to cochlear nerve fibers, near the first nodes of Ranvier (D2) and in the inner spiral bundle region (D1 and D2) where presynaptic olivocochlear terminals are found. No other receptor labeling was consistent. Cochlear function was normal in D3, D4 and D5 knockouts. D1 and D2 knockouts showed slight, but significant enhancement and suppression, respectively, of cochlear responses, both in the neural output (ABR wave 1) and in outer-hair cell function (DPOAEs). Vulnerability to acoustic injury was significantly increased in D2, D4 and D5 lines: D1 could not be tested, and no differences were seen in D3 mutants, consistent with a lack of receptor expression. The increased vulnerability in D2 knockouts was seen in DPOAEs, suggesting a role for dopamine in the OHC area. In D4 and D5 knockouts, the increased noise vulnerability was seen only in ABRs, consistent with a role for dopaminergic signaling in minimizing neural damage.

An investigation of hearing impairment in de-novo Parkinson's disease patients: A preliminary study

“…The hyperpolarized OHC membrane shows an electro-mechanical response which makes the assembly of OHC and Dieters cell more difficult thus reducing BM mobility and in turn sound amplification and DPOAE production. Recently, Maison et al [11] described collaterals of LOC efferent fibers making synapses, at the level of inner spiral bundle, on MOC efferent fibers traveling to OHC. Although specific dopamine receptors on MOC fibers have not yet been described, it is reasonable that DA may exert a modulatory effect on DPOAE at such a level.…”

Regulation of dopamine D2 receptors in the guinea pig cochlea

“…A combined RT-PCR and immunohistochemical studies suggested that all five DA receptors are present in the rat cochlear nerve [6]. A more recent immunohistochemical study in mice demonstrated that the D1 and D2 receptors were robustly expressed in cochlear nerve fibers in the neuropil beneath the IHCs, while D3, D4, and D5 receptor staining was weak and/or nonspecific [7]. This quantitative RT-PCR study suggested that D2 receptors were expressed at much higher levels than D1, D5, and D4, while D3 receptor expression was not detected.…”

Methionine Sulfoxide Reductase A Knockout Mice Show Progressive Hearing Loss and Sensitivity to Acoustic Trauma

“…4), which is a TTS-generating stimuli that evokes dopaminergic cochlear protection [Maison et al, 2012]. This suggests that dopaminergic neurons in MsrA knockout mice might be unable to modulate noise suppression [Maison et al, 2012], eliciting acoustic damage from even moderate to low levels of noise (Fig. 4).…”

“…Inoue et al [2006] demonstrated the expression of several dopamine receptors in the cochlear neurons beneath the inner hair cell region, and Darrow et al [2006] suggested that do- paminergic neurons from the olivocochlear nuclei extend beneath the inner hair cells to form dopaminergic endings. Alternatively, a recent study by Maison et al [2012] confirmed that mice lacking dopamine receptors exhibit exacerbated damage from acoustic trauma, indicating that dopaminergic innervations might act to minimize glutamate-induced excitotoxicity emanating from acoustic trauma. Interestingly, acoustic damage in MsrA knockout mice is evoked from a 15-min exposure to noise at a 94-dB SPL (Fig.…”

“…MsrA aids in the protection of the age-related complications in the central nervous system [Oien et al, 2008]. The MsrA gene is also involved in the maintenance of proper functions of the neurons in the brain's dopaminergic system, located within the olivary sections of the brain that projects their fibers in the cochlea and safeguards them from acoustic trauma [Darrow et al, 2006;Kwon et al, 2014b;Maison et al, 2012;Oestreicher et al, 1997]. Thus, MsrA knockout mice are better tools for examining the roles of MsrA in the ears of adult mice.…”