Effects of cochlear ablation on amino acid levels in the rat cochlear nucleus and superior olive

Abstract

Amino acids have important roles in the chemistry of the auditory system, including communication among neurons. There is much evidence for glutamate as a neurotransmitter from auditory nerve fibers to cochlear nucleus neurons. Previous studies in rodents have examined effects of removal of auditory nerve input by cochlear ablation on levels, uptake and release of glutamate in cochlear nucleus subdivisions, as well as on glutamate receptors. Effects have also been reported on uptake and release of γ-aminobutyrate (GABA) and glycine, two other amino acids strongly implicated in cochlear nucleus synaptic transmission. We mapped the effects of cochlear ablation on the levels of amino acids, including glutamate, GABA, glycine, aspartate, glutamine, taurine, serine, threonine, and arginine, in microscopic subregions of the rat cochlear nucleus. Submicrogram-size samples microdissected from freeze-dried brainstem sections were assayed for amino acid levels by high performance liquid chromatography. After cochlear ablation, glutamate and aspartate levels decreased by 2 days in regions receiving relatively dense innervation from the auditory nerve, whereas the levels of most other amino acids increased. The results are consistent with a close association of glutamate and aspartate with auditory nerve fibers and of other amino acids with other neurons and glia in the cochlear nucleus. A consistent decrease of GABA level in the lateral superior olive could be consistent with a role in some lateral olivocochlear neurons. The results are compared with those obtained with the same methods for the rat vestibular nerve root and nuclei after vestibular ganglionectomy.

Cochlear Damage Affects Neurotransmitter Chemistry in the Central Auditory System

“…There were also consistent decreases of GABA level in the rat LSO ipsilateral to cochlear ablation, which might result from a retrograde effect on olivocochlear neurons after destruction of their terminals ( 17 ). Measurements for GABA, especially GABA receptors, usually showed decreases after ototoxic drug administration.…”

“…After cochlear ablation, there were striking decreases of GABA levels in chinchilla VCN [which were bilateral ( 16 )], especially at shorter times (Table 4 ). In rat, there were [bilateral ( 17 )] decreases in AVCN but not in PVCN. There were similar but less striking decreases in chinchilla VCN GABA levels after carboplatin ( 12 ).…”

“…In superficial DCN, which receives little innervation from auditory nerve fibers ( 93 , 94 ), GABA levels surprisingly decreased in rat after cochlear ablation and in chinchilla after carboplatin administration. One possible explanation for these decreases in GABA levels could be non-specific effects of trauma ( 95 ), which would be produced by cochlear damage, since GABA is not substantially related to auditory nerve fibers ( 17 ). A transneuronal effect of cochlear ablation on GABA levels in ipsilateral CN neurons is supported by an immunohistochemical study in rats ( 96 ).…”

“…One study ( 6 ) found similar behaviorally measured tinnitus symptoms in chinchillas associated with three different patterns of cochlear damage following acoustic exposure, cisplatin, and carboplatin treatments. In our previous studies, we have found different effects on central auditory system neurotransmitter systems of different types of cochlear damage, including partial damage from acoustic trauma ( 7 – 10 ) and carboplatin treatment ( 11 , 12 ), both of which have been associated with tinnitus ( 2 , 13 ), and complete destruction via cochlear ablation ( 14 – 17 ). Cochlear ablation produces complete transection of auditory nerve fibers, which has been associated with tinnitus ( 18 , 19 ).…”

Distribution of Vesicular Glutamate Transporter 2 and Ionotropic Glutamate Receptors in the Auditory Ganglion and Cochlear Nuclei of Pigeons (Columba livia)

“…Inner hair cells use glutamate as an excitatory neurotransmitter that is sent to type I SG neurons (Eybalin, ; Niedzielski and Wenthold, ; Matsubara et al., ; Ruel et al., ). Like the inner hair cells, SG neurons are reportedly glutamatergic (Isaacson and Walmsley, ; Wang et al., ; Godfrey et al., , ; Kaneko et al., ; Zhou et al., ).…”