2017LinleyDPhD.pdf (6.17 MB)
The Influence of acoustic over-exposure on central auditory processing
thesis
posted on 2017-12-04, 09:55 authored by Deborah Marie LinleyIt is well established that exposure to loud sounds causes deafness by damaging the cochlea, however less is known about the effects of acoustic over-exposure (AOE) on the auditory pathway in the brain. Neurons of the lateral superior olive (LSO) located in the superior olivary complex (SOC) are amongst the first to receive binaural input, with excitatory input from the ipsilateral ear, and inhibitory input from the contralateral ear, via the medial nucleus of the trapezoid body (MNTB). This enables interaural level difference processing which is an important mechanism of sound localisation.
I have examined synaptic and intrinsic excitability of mouse LSO neurons using an in vitro brain slice preparation. Kv3 voltage-gated K+ channels contribute to intrinsic excitability and AP (action potential) repolarisation in the MNTB, yet little is known of their role in the LSO. I have shown expression of Kv3.1 and Kv3.3 (but absence of Kv3.2 and Kv3.4) and assessed their contribution to outward currents using whole cell patch clamp from wildtype and knockout mice. In contrast to the MNTB, the LSO require Kv3.3 for fast AP firing, suggesting that these subunits have specific physiological roles in these nuclei. At the synaptic level, I observed rapid acceleration of decay kinetics during the first 2 postnatal weeks.
Following AOE, LSO neurons showed little change in intrinsic excitability, although MNTB neurons became more excitable with reduced AP thresholds. Measurement of auditory brainstem responses (ABRs) gives an In Vivo assessment of hearing. Early ABR waves were delayed and reduced in amplitude after AOE. This deficit was compensated, so that the amplitude and latency of wave IV were indistinguishable from control mice, again demonstrating plasticity in the auditory brainstem. By examining both synaptic and intrinsic excitability, I have identified complimentary mechanisms which underlie hearing loss and compensation following sound over-exposure.
History
Supervisor(s)
Forsythe, IanDate of award
2017-11-17Author affiliation
Department of Neuroscience, Psychology and BehaviourAwarding institution
University of LeicesterQualification level
- Doctoral
Qualification name
- PhD