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Neutrophins and synaptic plasticity in the spinal cord

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Research objectives and content Brain derived neurotrophic factor (BDNF) is neurotrophic factor for sensory neurons of the dorsal root ganglia. In addition to its trophic role, it has recently been demonstrated that this factor can acutely modify the strength of synaptic connections. Here we aim to investigate the role BDNF plays in the plasticity displayed by neurones of the spinal cord. Using an in vitro electrophysiology preparation, the pharmacology of C-fibre evoked ventral root reflexes will be assessed in BDNF knockout mice. It is also planned to characterize a new BDNF promoter IV knockout animal that should confine BDNF deficits to the periphery and use this mouse to determine the function of BDNF after nerve injury. Gene transfer techniques are also being developed in the laboratory using the particle mediated system (Gene gun) to replace or overexpress missing gene products in order to rescue physiological deficits seen in the knockout mice. Training content (objective, benefit and expected impact) By training in Dr. Lewin's laboratory I will gain experience of working with transgenic animals and learn standard molecular biology techniques essential for the analysis of these animals. I will also have the opportunity to learn an important in vitro electrophysiology preparation. These new technical skills will enable me to more flexibly address important basic questions in my field eventually as an independent researcher. Links with industry / industrial relevance (22) The results of the present studies may well lead to the development of drug development strategies for the treatment of pain and sensory neuropathies associated with peripheral nerve injury.

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MAX DELBRUCK CENTER FOR MOLECULAR MEDICINE
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