Prof Mayank Dutia
Our current research interests are in the mechanisms of synaptic and neuronal plasticity in the vestibular system and cerebellum.
I was a Wellcome Research Training Scholar at the Institute of Physiology, University of Glasgow (1974-78), where I studied the properties and functions of muscle spindle and tendon organ afferents for my PhD, under the supervision of Prof Ian Boyd.
Subsequently, as an MRC Research Fellow, I investigated the interactions between vestibular and neck proprioceptive reflexes in the neck and forelimb muscles, also at Glasgow University.
I was appointed Lecturer in Physiology at Edinburgh in 1980, and continued my work on vestibular and neck reflexes with grant support from the MRC.
I extended this to include studies of the pharmacology and electrophysiology of vestibular nucleus neurons in brain slices in vitro, with support from the Wellcome Trust.
Our current research interests are in the mechanisms of synaptic and neuronal plasticity in the vestibular system and cerebellum:
- after de-afferentation of the inner ear ('vestibular compensation')
- in cellular mechanisms of 'motor learning'
- in the actions of stress steroids on brain function and plasticity
Disorders of balance
Disorders of balance are common, particularly in the elderly. The vestibular system (comprising the sensory receptors in the inner ear, the vestibular nuclei, cerebellum and related brain areas), is essential for postural stability, the control of eye movements, head-eye coordination, and stabilization of gaze.
Dizziness, vertigo, and loss of balance function through inner ear disease or brain lesions, have a major impact on the quality of life of affected patients. My lab investigates the mechanisms of adaptive plasticity in the vestibular system and cerebellum using a well-established animal model of inner ear disease. Our recent work has shown that changes in the sensitivity of vestibular nucleus neurones to the inhibitory transmiiter GABA, and changes in the intrinsic properties of vestibular neurones, are important brain compensatory mechanisms after inner ear damage.
In addition we have shown that this plasticity is modulated by stress hormones, so that the stress which normally accompanies vestibular dysfunction also promotes compensatory plasticity in the brain. Recently we showed that a site of action of stress hormones in modulating vestibular function is the cerebellar flocculus, and cerebellar cortical plasticity is required for the initiation of changes in intrinsic properties of the vestibular nucleus neurons.
Thus vestibular neuronal plasticity is a useful model of a form of cerebellar-dependent “motor learning”. Our current work uses a range of techniques, from microdialysis and HPLC analysis of neurotransmitter release, through in vivo and in vitro electrophysiology to proteomics, to extend these findings and further elucidate the mechanisms of vestibular function and plasticity. Further understanding may help in the development of evidence-based strategies for the management of balance disorders; and also reveal fundamental mechanisms of neuronal and synaptic plasticity in the brain, particularly in relation to cerebellar function in “motor learning”, and the role of stress steroids in modulating brain plasticity.
Understanding the biological basis of brain plasticity is also of great interest in the design and implementation of adaptive control systems in robotics and robot learning.
Recent reviews of our work
- Seemungal BM et al (2001) Current Opinion in Neurology 14: 27-34
- Smith PF (2001) Current Opinion in Neurology 13: 31-37
- Zhang W & Linden DJ (2003) Nature Reviews Neuroscience 4: 885 -900
Our current work is supported by grants from the Wellcome Trust, Biotechnology and Biological Sciences Research Council (BBSRC) and Engineering and Physical Sciences Research Council (EPSRC).
- Professor Paul Dean and Dr John Porrill, University of Sheffield, UK; Professor Chris Macheulish and Dr Tony Pipe, University of the West of England: Adaptive plasticity in vestibular neurons and its application to models of cerebellar function, and adaptive control algorithms in robotics (funded by EPSRC, Novel Computing Initiative)
- Professor Alastair Aitken, Professor Jonathan Seckl and Dr Janet Paterson, Edinburgh University: Proteomics of vestibular system and cerebellar plasticity (funded by the BBSRC, Proteomics and Cell Function Initiative)
- Dr Mike Ludwig and Dr Filip Bergquist, Edinburgh University: Microdialysis and HPLC analysis of factors controlling neurotransmitter release in the vestibular system and cerebellum (funded by the Wellcome Trust)
- Professor Richard Tham and Dr Anna Magnusson, University of Linkoping, Sweden: Mechanisms of vestibular compensation (funded by the Wellcome Trust)
- Professor Chris Yeo, University College London, UK: Mechanisms of cerebellar-dependent plasticity
- Dr Pierre Paul Vidal, Dr Nicolas Vibert, Dr Hans Straka and Dr Lee Moore, CNRS, Paris: Mechanisms of vestibular function and plasticity
- Professor Vito Enrico Pettorossi and Dr Silvarosa Grassi, University of Perugia, Italy: Mechanisms of vestibular function and plasticity
- Dr Maria Vittoria Podda, Universita Cattolica, Rome, Italy: Mechanisms of vestibular function and plasticity
Hospedales T, van Rossum MCT, Graham BP, and Dutia MB (2008) Implications of noise and neural heterogeneity for vestibuloocular reflex fidelity. Neural Computation 20:756-778.
Grassi S, Frondaroli A, Dieni C, Dutia MB, and Pettorossi VE (2007) Neurosteroid modulation of neuronal excitability and synaptic transmission in the rat medial vestibular nuclei. European Journal of Neuroscience 26: 23-32.
Wishart TM, Paterson JM, Short DM, Meridith S, Robertson KA, Sutherland C, Cousin MC, Dutia MB, and Gillingwater TH (2007) Differential proteomic analysis of synaptic proteins identifies potential cellular targets and protein mediators of synaptic neuroprotection conferred by the slow Wallerian degeneration (Wlds) gene.Molecular and Cellular Proteomics 6(8):1318-1330.
Paterson J, Short D, Flatman PW, Seckl JR, Aitken A, and Dutia MB (2006) Changes in protein expression in the rat medial vestibular nuclei during vestibular compensation. Journal of Physiology 575(3): 777-788.
- Symposium on Vestibular Mechanisms and Plasticity, Hawaii, USA 1999
- Solvay Pharma Symposium on Meniere’s Disease, Paris, France 1999
- British Society for Audiology, Annual Meeting, Buxton, UK 1999
- 3rd Forum of European Neuroscience Societies (FENS), Paris 2002
- Symposium on Mechanisms of Vestibular Compensation, Annual Meeting of the Barany Society, Seattle, 2002
- Symposium on Cerebellar Mechanisms, Orcas Island, 2002
- Society for the Neural Control of Movement Annual Meeting, Santa Barbara, 2003
- British Academic Conference in Otolaryngology, 2003
- Workshop on Vestibular Compensation, Edinburgh 2003
- Association for Research in Otolaryngology Annual Meeting, New Orleans, USA February 2005
- Symposium on the Neural Basis of Motor Learning and Performance: from cell to function. Satellite Meeting of the Society for the Neural Control of Movement, Carmona, Spain 2007