Project description
Solving the puzzle of synaptic protein numbers regulation
Neurons regulate dendritic protein numbers and redistribute proteins in response to synaptic changes. However, the way the available pool of proteins is redistributed via diffusion or active trafficking and how synaptic protein numbers are modified by increased translation of local mRNAs is a mystery. The EU-funded MolDynForSyn project aims to develop a data-driven theory describing the dendritic mRNA and protein distributions and use it to study the synaptic plasticity dynamics in dendrites and their impact on memory storage. The unique combination of theoretical and experimental data will result in a better understanding of long-term memory mechanisms and many neurological diseases associated with neuronal trafficking pathologies or protein synthesis dysfunction.
Objective
Proteins are the building blocks of life and neurons constantly need proteins to remain functional. This is a formidable challenge because neurons must regulate dendritic protein numbers across hundreds of micrometers, and need to redistribute proteins quickly in response to any synaptic changes. For example, long-term plasticity requires new proteins. Yet, it is still a puzzle how the available pool of proteins is redistributed via diffusion or active trafficking and how synaptic protein numbers are modified by increased translation of local mRNAs. Similarly, it is now an open question how the dysregulation of mRNA transport translates into plasticity impairments, how these modify circuit functions and ultimately lead to cognitive impairments. To answer these questions and connect the molecular dynamics to circuit function, we will develop a data-driven theory describing the dendritic mRNA and protein distributions in space and time and will use it to study the emergent synaptic plasticity dynamics in dendrites and its impact on memory storage. We will use data from leading experimental labs to identify how the unique combination of dendritic mRNAs, dendritic morphology, and synaptic activity gives rise to the synaptic protein dynamics that shapes circuit function. Our theory framework will generate and test hypotheses about how individual components such as mRNA motion, translation or degradation shape the protein exchange between synapses and clarify how they translate into multi-synapse synaptic plasticity rules that give rise to memory formation, memory generalization and separation. The unique combination of theory and experimental data will improve our understanding of long-term memory mechanisms and numerous neurological diseases that are associated with neuronal trafficking pathologies or protein synthesis dysfunction.
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Funding Scheme
ERC-STG - Starting GrantHost institution
53127 Bonn
Germany