Dr Martine Hamann

Tel: 0116 252 3074 Email: mh86@le.ac.uk

Cellular and Physiological Basis
Of Hearing and Balance Disorders

My lab is studying the neuronal mechanisms underlying hearing loss and tinnitus in response to exposure to loud sound. The aim is to identify new pharmacological targets against hearing loss and tinnitus and also to identify non pharmacological experimental procedures that will lead to improvement in those auditory defects.

Background

Hearing disorders are very common and can affect individuals of all ages. Of the UK adult population aged 18–60 years, 17% suffer significant hearing loss and this figure rises steeply with age (80% by 80 years is called presbycusis or hearing loss associated with aging).

There are two main types of hearing loss: conductive and sensorineural. Conductive hearing loss usually results from a blockage in the outer or middle ear, such as a build-up of excess ear wax or fluid from an ear infection. Therefore sound is incompletely transferred via the ossicular chain and is unable to reach the inner ear.

Conductive hearing loss can result from an abnormality in the structure of the outer ear, ear canal or middle ear – or be due to a ruptured eardrum and can often be corrected with minor surgery.

Sensorineural hearing loss results from damage to the hair cells within the cochlea or to the auditory nerve (or both). Damage to the cochlea occurs naturally as part of the ageing (presbycusis) but other main factors cause sensorineural hearing loss such as regular and prolonged exposure to loud sounds or loud music; ototoxic drugs (certain types of antibiotics); infectious diseases (rubella); complication at birth or brain injuries; tumours on the auditory nerve; genetic predisposition. Sensorineural hearing loss is for the moment irreversible and cannot be cured as damaged cochlear hair cells remain damaged for the rest of a person’s life. Projects in the lab. involve identifying neuronal markers that are modulated after acoustic over exposure and target those markers with pharmacological and non pharmacological means.

High voltage activated potassium currents, targets against hearing loss or tinnitus?

Pilati et al., Hearing Research 283 (2012) pages 98-106

This publication shows that exposure to loud sound triggers hearing loss and this is correlated with profound changes in the first relay in the central auditory pathway (the dorsal cochlear nucleus). Bursts observed in fusiform cells in this structure (figure below) are related to a down regulation of high voltage activated potassium currents. Bursts could underlie the abnormal hyperexcitability observed in the central auditory system during tinnitus.

http://www.ncbi.nlm.nih.gov/pubmed/22085487

http://globalmedicaldiscovery.com/key-scientific-articles/acoustic-over-exposure-triggers-burst-firing-in-dorsal-cochlear-nucleus-fusiform-cells/

Past group members:

Nadia Pilati - PhD GlaxoSmithKline

Present group members:

Matthew Barker - M.Phil student

Thomas Tagoe - PhD RNID

Publications relevant to the current projects :

Barker M, Billups B. and Hamann M. (2009) Focal macromolecule delivery in neuronal tissue using simultaneous pressure ejection and local electroporation. J. Neurosci. Methods 15:273-84.
Pilati N, Barker M, Panteleimonitis S, Donga R. and Hamann M. (2008) A rapid method combining Golgi and Nissl staining to study neuronal morphology and cytoarchitecture. J Histochem Cytochem. 56:539-550.
Song P, Yang Y, Barnes-Davies M, Bhattacharjee A, Hamann M, Forsythe ID, Oliver DL and Kaczmarek LK. (2005) Acoustic environment determines phosphorylation state of Kv3.1 potassium channel in auditory neurons. Nat. Neurosci. 8: 1335-1342.
Hamann M., Billups B. and I. F. Forsythe (2003) Non-calyceal excitatory inputs mediate low fidelity synaptic transmission in rat auditory brainstem slices. Eur. J. Neurosci. 18: 2899-2902.

Other publications :

Hamann M., Gibson A., Davies N., Walhin J.P., Partington L., Trezise D. And Main M. (2009). Human ClCla1 modulates anion conduction of calcium activated chloride currents. J. Physiol. (Lond.) 15: 2255-74.
Furness DN, Dehnes Y, Akhtar AQ, Rossi DJ, Hamann M, Grutle NJ, Gundersen V, Holmseth S, Lehre KP, Ullensvang K, Wojewodzic M, Zhou Y, Attwell D, Danbolt NC.(2008) A quantitative assessment of glutamate uptake into hippocampal synaptic terminals and astrocytes: new insights into a neuronal role for excitatory amino acid transporter 2 (EAAT2). Neuroscience 157: 80-94.
Hamann M., Rossi D.J., Mohr C., Andrade A.L. and D. Atwell (2005) The electrical response of cerebellar Purkinje neurons to simulated ischaemia. Brain. 128: 2408-2420.
P. Cavelier, M. Hamann, D. Rossi, P. Mobbs and D. Attwell (2005) Tonic excitation and inhibition of neurons: ambient transmitter. Sources and computational consequences. Prog. Biophys. Mol. Biol. 87:3-16.
Rossi DJ, Hamann M and Attwell D. (2003) Multiple transmitter release modes activate GABA-A receptors in cerebellar granule cells. J. Physiol.(Lond.) 548: 97-110.
Hamann M., Rossi D.J. and D. Attwell (2002) Tonic and spillover inhibition of granule cells control information flow through cerebellar cortex. Neuron 33, 625-633.
Hamann M., Rossi D.J., Marie H. and D. Attwell (2002) Knocking out the glial glutamate transporter GLT-1 reduces glutamate uptake but does not affect hippocampal glutamate dynamics in early simulated ischaemia. Eur. J. Neurosci. 15: 1-8.