Description
Modifiability of neuronal connectivity by formation of new synapses, and alteration of the strength and stability of existing synapses, is regarded as the main cellular basis for memory. The genes encoding neurotrophin BDNF and activity-regulated cytoskeleton-associated protein ARC are the master genes of synaptic plasticity. The objective of this project is to study neuronal activity-regulated expression of BDNF and Arc genes in the nervous system. The project is expected to achieve new knowledge about the molecular mechanisms of synaptic plasticity and memory by taking advantage of the complementary expertise of the groups of prof. Tõnis Timmusk, Tallinn University of Technology, and the donor partner prof. Clive Bramham, University of Bergen. The main target groups are PhD and postdoctoral students. The project and partnership have positive impact on the internationalization of R&D and higher education by attracting foreign competence to Estonia.
Summary of project results
Modifiability of neuronal connectivity by formation of new synapses, and alteration of the strength and stability of existing synapses, is regarded as the main cellular basis for memory and long-term behavioral adaptations. The genes encoding neurotrophin BDNF and activity-regulated cytoskeleton-associated protein ARC are considered to be the master genes of synaptic plasticity. In addition, BDNF has received particular interest for its deregulation in nervous system disorders. Therefore knowledge about the regulatory mechanisms of BDNF gene is important both for understanding of nervous system function and for finding new drug targets. The aim of this project was to study the molecular mechanisms of neuronal activity-regulated expression of BDNF and Arc genes, including transcription, mRNA localization, and translation, in the nervous system. The experimental approach took advantage of the complementary know-how and expertise of the groups of Prof. T. Timmusk, Tallinn University of Technology, in BDNF gene structure, expression and transcriptional regulation and Prof. C. Bramham, University of Bergen, in BDNF and Arc function in vivo, electrophysiology, imaging and translational regulation. Novel mechanisms regulating neuronal activity- and TrkB signaling-dependent transcription and translation of BDNF and Arc genes in nerve cells were identified and characterized. The output of the project represents a very relevant contribution to the understanding of BDNF physiology, and in particular the role of the neurotrophin in synaptic plasticity.
Summary of bilateral results
The different but complementary expertise of Tallinn and Bergen research groups has enabled carry out this project. The two groups involved in the project have complementary expertise which is a major strength of the project. Prof. T. Timmusk has a very good track record of publication on the regulation of BDNF gene expression, while Prof. C. Bramham has been focusing on the role of BDNF in long-term synaptic potentiation. Project partner’s main technical and professional contribution to the project was planning and carrying out experiments, particularly the in vivo animal experiments. The partnership has significantly contributed to strengthening bilateral relations between the partner labs by several visits, Skype conferences and e-mail correspondence that enabled discussions of project experimental plans and results. Importantly, the project partnership has helped to start to build up wider international cooperation in the field of neurotrophins and synaptic plasticity. The project sustainability is very good since many collaborative experiments are ongoing and several articles are planned to be published based on the results obtained. In addition, joint proposals are planned to be submitted to European financing initiatives.