Molecular mechanisms for activity-dependent control of neuronal excitability in the central auditory pathway

Department of Neuroscience, Psychology & Behaviour, University of Leicester, LE1 9HN, UK

Sustained exposure to loud sounds (or noise) causes loss of peripheral synapses from inner hair cells (Kujawa & Liberman, 2015) this degrades information transmission and is thought to underlie ‘hidden hearing loss’. But are there contributions further downstream at synapses in the brain? We have recently shown that acoustic overload reduces the expression of those glutamate receptor subunits with the fastest time-course (Pilati et al., 2016) causing synaptic responses to slow for a period of weeks after the exposure. Associated with this, synaptic activity also adapts neuronal excitability (Tong et al., 2013).

This project will employ electrophysiological methods, along with molecular and genetic tools to examine how sound over-exposure changes synaptic transmission and neuronal excitability. We will test the hypothesis that the processes involved in homeostatic control of neuronal excitability contribute to the generation of hyper-excitability and underlie perception of phantom sounds and tinnitus in the brain. We expect to gain knowledge of how sound trauma causes hearing dysfunction and of how novel therapeutic approaches can mitigate these symptoms.

This project involves exchange and collaborative links across Europe. The host and partner institutions will provide training and expertise in all aspects of the study. We are looking for an ambitious young scientist with a flair for innovation and with a strong work ethic. The successful candidate will demonstrate evidence of fostering European connections. S/he will learn to apply electrophysiological, immunohistochemical and molecular methods, along with optogenetic and gene editing to study synaptic transmission and neuronal excitability in the context of central auditory processing. You will join a team of neuroscientists working together in the Dept of Neuroscience, Psychology & Behaviour that employ complementary techniques, and the LISTEN Consortium which operates across the breadth of Europe.

References

• Kujawa SG & Liberman MC (2015). Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss. Hear Res 330, 191–199.
• Pilati N, Linley DM, Selvaskandan H, Uchitel O, Hennig MH, Kopp-Scheinpflug C & Forsythe ID (2016). Acoustic trauma slows AMPA receptor-mediated EPSCs in the auditory brainstem, reducing GluA4 subunit expression as a mechanism to rescue binaural function. J Physiol (Lond) 594, 3683–3703.
• Tong H, Kopp-Scheinpflug C, Pilati N, Robinson SW, Sinclair JL, Steinert JR, Barnes-Davies M, Allfree R, Grubb BD, Young SM & Forsythe ID (2013). Protection from noise-induced hearing loss by Kv2.2 potassium currents in the central medial olivocochlear system. Journal of Neuroscience 33, 9113–9121.

Prof. Ian D. Forsythe

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