Objective
Abatement or loss of inner ear function is a major health problem since more than 10% of the population suffer from hearing disorders, a large majority of which arise from damage to the sensory-neuronal elements of the inner ear. In humans, damage to hair cells or sensory neurons are often permanent and lead to severe limitations in our ability to function in society. In the recent past, a number of research teams, mostly situated in the United States have concentrated their work on the newly discovered regenerative properties of the neuro-sensory elements of the inner ear. These studies carry an understandably large amount of hope but are suffering from a the lack of basic knowledge on the development of inner ear sensory systems and from the absence of an experimental paradigm that would permit to study directly the processes and factors involved in development, impairement and regeneration.
Regeneration of sensory function in the inner ear not only needs repair or replacement of both hair cells and nerve endings, it also requires re-establishment of functional synaptic connections between them. Basic knowledge on how synaptic connectivity is established during development and on how it could happen or could be triggered to happen during regeneration is urgently needed. Two of the partners of this project have collaborated closely to the establishment of in vitro models of the inner ear where, using confocal microscopy and electrophysiology, direct investigations of the 3D cellular structure and of the function of inner ear receptors is made possible. The two other partners have pioneered the fields of - the neurotrophin family of trophic factors using molecular biology techniques and of -the mechanisms of synaptic release of neurotransmitters using protein analysis and physiology techniques. In recent years, roles have been proposed for trophic factors in regulating many phenomena, such as synaptogenesis, synaptic transmission, nerve guidance, regeneration, and as instructive/perrnissible factors in cell differentiation. Neurotrophins are endogenous inner ear trophic factors intimately involved in the development and survival of sensory neurons.
Our goal is to combine the expertise of these four European research groups in a joined effort to better understand the tropic and trophic mechanisms that lead to the correct establishment of synaptic connectivity in the inner ear during development and to study how these mechanisms can be triggered to re-establish this connectivity after lesion in the adult animal. Using a combination of techniques such as time-lapse confocal microscopy, on stage cellular and organotypic culture and electro-physiology, we believe that the continuous monitoring, in a single experimental lun, of these processes is possible. The use of inner ear tissue collected from animals in which the expression of neurotrophins has been altered by gene targeting techniques (knock-out and knock-in) will give us a better understanding of the role of these trophic factors and will lead to an evaluation of their potential use in preserving and restoring inner ear function.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine physiology
- natural sciences physical sciences optics microscopy confocal microscopy
- natural sciences biological sciences molecular biology
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Coordinator
34095 Montpellier
France
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