Auditory neurobiology

Research in this laboratory has focused on the regulation of purinergic signalling in the inner ear. Purinergic (ATP) signalling can induce a number of actions in cochlear tissues. Ectonucleotidases are enzymes that regulate ATP concentrations in the cochlea by breaking it down to adenosine and provide a termination mechanism for purinergic signalling and purine recycling after adenosine re-uptake. Ectonucleotidase activity in the cochlea is largely mediated by E-NTPDase family of enzymes. Our group was the first to show E-NTPDase activity in the cochlea and demonstrate its role in pathophysiology of noise-induced cochlear injury. Increased activity of these ecto-enzymes may reflect adaptive response of cochlear tissues to limit ATP signalling during noise exposure and thus protect the cochlea.

Our current research efforts are aimed to assess auditory function in NTPDase knockout mice and characterise their cochlear response to ATP and noise. More recent work has been directed at the characterization of NTPDase2 isoforms produced by alternative splicing of the rat NTPDase2 gene. We are also investigating the role of soluble NTPDases in hearing and the putative role of adenosine in cochlear protection.

1. Cochlear function in NTPDase knockout / transgenic mice
2. The role of soluble NTPDases in the cochlea NTPDase trafficking in CHO cells
3. Adenosine receptors and transporters in the cochlea

• A/Prof Gary D. Housley (Department of Physiology, the University of Auckland)
• A/Prof Peter Thorne (Department of Physiology, the University of Auckland)
• Dr Christian Soeller (Department of Physiology, the University of Auckland)
• A/Prof Simon Robson (Harvard University , Boston, USA)
• Dr Jean Sévigny (University of Laval , Quebec, Canada)
• Prof Herbert Zimmermann (Goethe University , Frankfurt, Germany)
• Prof LA Pinna (University of Padova, Italy)

• Cochlear biochemistry and immunohistochemistry
• Molecular biology
• Cell biology

1. Vlajkovic S.M., Vinayagamoorthy A., Thorne P.R., Robson S.C., Wang C.J.H., Housley G.D. Noise-induced up-regulation of NTPDase3 expression in the rat cochlea: implications for auditory transmission and cochlear protection (in press)
2. Wang C.J.H., Vlajkovic S.M., Housley G.D., Braun N., Zimmermann H., Robson S.C.,Sévigny J., Soeller C., Thorne P.R. C-terminal splicing of NTPDase2 provides distinctive catalytic properties, cellular distribution and enzyme regulation. Biochem. J. 385(3), 729-736, 2005
3. VLAJKOVIC S.M. , HOUSLEY G.D., MUÑOZ D.J.B., ROBSON S.C., SÉVIGNY J., WANG C.J.H., THORNE P.R. Noise exposures induce upregulation of ecto- nucleoside triphosphate diphosphohydrolases 1 and 2 in rat cochlea. Neurosci. 126, 763-773, 2004
4. VLAJKOVIC, S.M ., THORNE, P.R., SEVIGNY, J., ROBSON , S.C. , HOUSLEY, G.D. Distribution of ecto-nucleoside triphosphate diphosphohydrolases 1 and 2 in rat cochlea. Hear. Res. 170, 127-138, 2002
5. VLAJKOVIC, S.M ., THORNE, P.R., SEVIGNY, J., ROBSON , S.C. , HOUSLEY, G.D. NTPDase1 and NTPDase2 immunolocalisation in mouse cochlea: implications for regulation of P2 receptor signalling. J. Histochem. Cytochem.50, 1435-1441
6. JÄRLEBARK, L.E., HOUSLEY, G.D., RAYBOULD, N.P., VLAJKOVIC, S.M, THORNE, P.R. ATP-gated ion channels assembled from P2X2 receptor subunits in the mouse cochlea. NeuroReport 13, 1979-1984, 2002
7. THORNE, P.R., MUÑOZ, D.J.B. , NIKOLIC, P., MANDER, L., JAGGER, D.J., GREENWOOD, D., VLAJKOVIC, S.M., HOUSLEY, G.D. Potential role of purinergic signalling in cochlear pathology. Audiol. Neurootol. 7, 180-184, 2002
8. HOUSLEY, G.D., JAGGER, D.J., GREENWOOD , D., RAYBOULD, N.P., SALIH, S.G., JÄRLEBARK, L.E., VLAJKOVIC, S.M., KANJHAN, R., MUÑOZ, D.J.M., THORNE, P.R. Purinergic regulation of sound transduction and auditory neurotransmission. Audiol. Neurootol. 7, 55-61, 2002
9. VLAJKOVIC, S.M., HOUSLEY, G.D., CHRISTIE, D.L., GREENWOOD , D., NIKOLIC, P., BEAUDOIN, A.R. AND THORNE, P.R.The role of ecto-NTPDases in cochlear function. In: Ecto-ATPases and Related Ectonucleotidases. L. Vanduffel, R. Lemmens (Eds.), Shaker Publishing B.V, Maastricht , pp 136-144. 2000