Disruption of Lateral Olivocochlear Neurons via a Dopaminergic Neurotoxin Depresses Sound-Evoked Auditory Nerve Activity

Abstract

We applied the dopaminergic (DA) neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the guinea pig cochlear perilymph. Immunolabeling of lateral olivocochlear (LOC) neurons using antibodies against synaptophysin was reduced after the MPTP treatment. In contrast, labeling of the medial olivocochlear innervation remained intact. As after brainstem lesions of the lateral superior olive (LSO), the site of origin of the LOC neurons, the main effect of disrupting LOC innervation of the cochlea via MPTP was a depression of the amplitude of the compound action potential (CAP). CAP amplitude depression was similar to that produced by LSO lesions. Latency of the N1 component of the CAP, and distortion product otoacoustic emission amplitude and adaptation were unchanged by the MPTP treatment. This technique for selectively lesioning descending LOC efferents provides a new opportunity for examining LOC modulation of afferent activity and behavioral measures of perception.

Physiology, pharmacology and plasticity at the inner hair cell synaptic complex

“…This LSO lesion resulted in a significant depression of the CAP amplitude (Le Prell et al, 2003). A similar effect was found when the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was applied to the round window membrane of the cochlea (Le Prell et al, 2005). On the contrary, when LOC efferents were activated by electrical stimulation of the inferior colliculus (IC), gross and single unit auditory nerve responses were either enhanced or suppressed, while cochlear responses dominated by OHCs, such as otoacoustic emissions and cochlear microphonics remained unchanged (Groff and Liberman, 2003;Mulders and Robertson, 2005).…”

Brainstem Auditory Evoked Potentials Suggest a Role for the Ventral Cochlear Nucleus in Tinnitus

“…One possibility is that there was diffuse loss of inner hair cells in the tinnitus subjects compared with their matched, nontinnitus counterparts, which was not sufficient to manifest as an elevated mean threshold for the tinnitus subjects but was nevertheless sufficient to result in a lowered wave I amplitude. Another possibility is that inner hair cells, and also ANFs, were equally intact in tinnitus and closely matched non-tinnitus subjects, but excitability of ANFs was reduced via the lateral olivocochlear efferents which terminate on their endings (Le Prell et al 2003, 2005. Yet another possibility is that the inner hair cell population was equally intact in tinnitus subjects and matched, non-tinnitus subjects, but there was (1) diffuse loss of ANFs that was sufficient to manifest as a reduction in mean wave I amplitude but not a threshold elevation in tinnitus subjects and/or (2) loss of higher-threshold ANFs but not the lowest threshold fibers determining behavioral threshold.…”

Disruption of lateral olivocochlear neurons with a dopaminergic neurotoxin depresses spontaneous auditory nerve activity

“…Data from lesion [15, 17, 21, 48, 50], electrical stimulation [10], and gene knockout [27-30, 45] studies suggest several potential functional roles for LOC neurons. LOC modulation of AN activity may support interaural level comparisons necessary for accurate sound localization [2, 10], including relearning of localization tasks after unilateral conductive hearing loss [11].…”

“…In contrast, lesions of the medial and lateral limb of mouse LSO resulted in 30-50% increases in amplitude of wave I of the sound-evoked auditory brainstem response (ABR) [3]. A second method for disrupting LOC efferents is application of the DA neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the round window membrane (RWM) [15]. MPTP is metabolized to MPP+ and taken up pre-synaptically by neurons containing DA; accumulation of MPP+ results in mitochondrial dysfunction, oxidative stress, and neuronal death [31, 43].…”