Dynamics and regulation of denervation-induced dendritic plasticity of dentate granule cells

• Applicant: Professor Dr. Thomas Deller
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2005 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 19698450

Neurons which are denervated following brain injury are reinnervated by afferent fiber systems terminating in their vicinity. During this process they remodel their dendritic tree: spines and dendrites atrophy upon denervation and are reconstructed upon reinnervation. Although lesion-induced dendritic plasticity has long been described, neither the dynamics nor the mechanisms regulating dendritic reorganization have yet been understood. As far as dendritic atrophy is concerned, it is believed that glutamate released from degenerating terminals elevates intracellular Ca2+, which in turn degrades the cytoskeleton. To which extent intracellular or extracellular Ca2+-pools contribute to this process is unknown. Similarly, the molecular players regulating dendritic reconstruction are unidentified. Therefore, this project aims to (1) characterise the dynamics of lesion-induced plasticity of dentate granule cells in vitro and in vivo using EGFP-mouse mutants, (2) study the role of intracellular and extracellular Ca2+ for postlesional dendritic atrophy using an in vitro model and mutant mice lacking spine-specific Ca2+-stores (synaptopodin -/- mice), (3) investigate the role of BDNF in postlesional dendritic remodelling, and (4) identify new regulatory molecules involved in the reconstruction of dendrites and spines following reinnervation using laser microdissection and cDNA array techniques.

• DFG Programme: Research Grants