Hamann Neuroscience Group
Acute or chronic noise can damage the cochlea, initiating a series of plastic changes within the central auditory pathways that contribute to hearing loss and sometimes to the emergence of tinnitus, the perception of sound in the absence of acoustic stimulation. We are combining computational modelling, in vitro field potential and whole cell patch clamp recordings in the auditory brainstem dorsal cochlear nucleus with quantitative behavioural analyses to study cellular mechanisms associated to hearing loss and tinnitus.
- We developed a focal macromolecule delivery method in neuronal tissue (Barker al., 2009, Journal of Neuroscience Methods. 177:273-84) to demonstrate synaptic connections between the vestibular system and the dorsal cochlear nucleus (Barker et al., 2012, PLoS oNE. 7(5):e35955). After exposure to loud sound we showed that the expression level of vesicular glutamate transporters (V-GLUT) originating from auditory nerve fibres (VGLUT-1) was decreased whereas the expression level of V-GLUT2 originating from the lateral vestibular nucleus was increased.
Amplification of VGLUT-2 expression after acoustic overexposure could be a compensatory mechanism from vestibular inputs in response to hearing loss and to a decrease of VGLUT-1 expression from auditory nerve findings
- Previous studies have shown that exposure to loud sound leads to abnormal electrical activity in the dorsal cochlear nucleus that could underlie tinnitus. In a collaborative study with Dr Charles Large (Autifony Therapeutics Ltd), we have shown that one of the changes in the central nervous system following exposure to loud sound is the reduced function of Kv3 K+ channels in the auditory brainstem leading to bursting activity in principal cells (Pilati et al. 2012, Hearing Research 283:98-106, study funded by Deafness Research UK and Medisearch).
A current MRC Industrial Case Studentship with Autifony Therapeutics Ltd aims at investigating some of Autifony's compounds on synaptic transmission and plasticity in the auditory brainstem dorsal cochlear nucleus.
- We have shown that exposure to loud sound reduced the number of myelinated auditory nerve fibres in the cochlea and decreased the firing rate of principal within the dorsal cochlear nucleus. Effects on firing rates were reproduced using a Leaky Integrate and Fire model implemented in MATLAB (Mathworks) by Dr Matias Ison ( Engineering Department, University of Leicester) (Pilati et al. 2012, Proceedings National Academy Sciences USA. 109:8292-7), Study funded by a GlaxoSmithkline PhD studentship to Nadia Pilati).
A PhD studentship granted by Action on Hearing Loss allowed further investigating how dysmyelination related to hearing loss affected synaptic transmission in the auditory brainstem dorsal cochlear nucleus (Tagoe et al., submitted for publication).
• The gap detection startle reflex paradigm has become a key component of our research to screen for tinnitus (study initially funded by Action on Hearing Loss followed by a 7 month post doctoral research grant funded by Nottingham-Leicester Hearing Loss and Tinnitus Neuroscience Consortium and the Department of Cell Physiology and Pharmacology, University of Leicester). The original device has been kindly donated by Michael Kinder (Kinder Scientific) and useful technical advice were provided by Michael Kinder and Jeremy Turner. Studies are in progress.
Action on Hearing Loss: http://www.actiononhearingloss.org.uk/
Fact sheets about tinnitus can be downloaded at: http://www.actiononhearingloss.org.uk/supporting-you.factsheets-and-leaflets.aspx
Deafness Research UK: http://www.deafness research.org.uk/
American Tinnitus Association: http://www.ata.org/
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