Choline acetyltransferase activity in the hamster central auditory system and long‐term effects of intense tone exposure

Abstract

Acoustic trauma often leads to loss of hearing of environmental sounds, tinnitus, in which a monotonous sound not actually present is heard, and/or hyperacusis, in which there is an abnormal sensitivity to sound. Research on hamsters has documented physiological effects of exposure to intense tones, including increased spontaneous neural activity in the dorsal cochlear nucleus. Such physiological changes should be accompanied by chemical changes, and those chemical changes associated with chronic effects should be present at long times after the intense sound exposure. Using a microdissection mapping procedure combined with a radiometric microassay, we have measured activities of choline acetyltransferase (ChAT), the enzyme responsible for synthesis of the neurotransmitter acetylcholine, in the cochlear nucleus, superior olive, inferior colliculus, and auditory cortex of hamsters 5 months after exposure to an intense tone compared with control hamsters of the same age. In control hamsters, ChAT activities in auditory regions were never more than one-tenth of the ChAT activity in the facial nerve root, a bundle of myelinated cholinergic axons, in agreement with a modulatory rather than a dominant role of acetylcholine in hearing. Within auditory regions, relatively higher activities were found in granular regions of the cochlear nucleus, dorsal parts of the superior olive, and auditory cortex. In intense-tone-exposed hamsters, ChAT activities were significantly increased in the anteroventral cochlear nucleus granular region and the lateral superior olivary nucleus. This is consistent with some chronic upregulation of the cholinergic olivocochlear system influence on the cochlear nucleus after acoustic trauma.

Serotonin modulates response properties of neurons in the dorsal cochlear nucleus of the mouse

“…Our finding that exogenously applied 5-HT increased spiking for the majority of fusiform cells in vivo is in line with this view, although tinnitus likely arises due to a combination of factors. For example, a trauma-related decrease in the strength of synaptic inhibition could lead to the hyperactivity of fusiform cells thought to underlie tinnitus (Wang et al, 2009; Middleton et al, 2011), as could an increase in activation of the cholinergic system (Jin et al, 2006; Godfrey et al, 2013). The present study provides a framework to further examine how 5-HT and other transmitters systems contribute to auditory processing in normal and impaired listening states.…”

Chronic tinnitus and unipolar brush cell alterations in the cerebellum and dorsal cochlear nucleus

“…Mechanisms that underpin compensatory processes are poorly understood. They may involve down-regulation of inhibitory neurotransmission mediated by γ-amino butyric acid (GABA) (Wang et al, 2011), and/or up-regulation of excitatory neurotransmission mediated by glutamic acid (Glu) (Brozoski et al, 2013; Tzounopoulos et al, 2004; Zeng et al, 2009), or modulation by other transmitter systems, such as acetylcholine (Deng et al, 2015; Godfrey et al, 2013; Schofield et al, 2011). Current research suggests that tinnitus dysfunction is distributed in the central auditory system (Knipper et al, 2013; Rauschecker, 1999; Roberts et al, 2010) and that additionally it involves areas outside of the traditionally-defined auditory pathway (Langguth et al, 2007; Lanting et al, 2009).…”

Cochlear Damage Affects Neurotransmitter Chemistry in the Central Auditory System

“…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 ).…”

“…Although taurine is not well established as an inhibitory neurotransmitter, there is evidence that taurine, in addition to its relatively high levels in glia ( 42 , 56 ), is closely associated with GABAergic and glycinergic neurotransmission and may act as an agonist at GABA and glycine receptors ( 57 – 59 ). Available evidence suggests that acetylcholine serves as a neurotransmitter for several centrifugal pathways of the auditory system, particularly olivocochlear and olivo-CN connections ( 10 , 35 , 36 , 60 , 61 ). Its effects are mostly excitatory in the CN ( 62 , 63 ) as well as other locations ( 64 ), and it may function as a neuromodulator as well as a neurotransmitter ( 64 ).…”