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Mechanisms of Microglia Synapse Communication

Project description

Uncovering the dialogue of microglia and neurons

Microglia represent the mediator of synapse formation or link between pre- and post-synapse, sensing neurotransmitter release at highly active pre-synaptic sites and actively orchestrating the formation of new spines from the dendrite. This is the main hypothesis of the EU-funded MicroSynCom project. It will investigate and reveal the underlying mechanisms of this process. The project will use two-photon stimulated emission depletion microscopy, novel viral and genetically encoded sensors for neurotransmitters, and optogenetic and chemogenetic manipulation tools. It will also combine these methods with the behaviour test in freely moving but also head-fixed mice to visualise microglia-mediated synapse formation in awake mice. For the first time, researchers will be able to uncover the mechanisms establishing this novel role of microglia as the mediator of synapse formation in live animals.

Objective

Microglia are the resident tissue macrophages of the brain and represent cells of the innate immune system. Looking at microglia from the immunological perspective, much is known about their role during inflammatory processes, factors that activate them and how they response e.g by releasing cytokines to mount an inflammatory response. This response has been shown to be detrimental during disease processes and lead to pruning/loss of synapses, a task microglia carry out also during development. Although microglia obviously play an important role in synaptic pruning and loss, it remains an open question, whether microglia are involved in the process of synapse formation under physiologic conditions. Therefore, the main hypothesis of MicroSynCom is that microglia represent the mediator of synapse formation or linker between pre- and post-synapse: sensing neurotransmitter release at highly active pre-synaptic sites and actively orchestrating the formation of new spines from the dendrite. I propose to investigate and reveal the underlying mechanisms of this tripartite microglia synapse communication process. Therefore, we will use two-photon stimulated emission depletion microscopy (2P-STED), novel viral and genetically encoded sensors for neurotransmitters, as well as optogenetic and chemogenetic manipulation tools. These methods will be combined with behavior test in freely moving, but also head-fixed mice to visualize microglia mediated synapse formation in awake mice. This will allow us for the first time to visualize, investigate and reveal the mechanisms establishing this novel role of microglia as the mediator of synapse formation in life animals and relate it to physiologically relevant neuronal network rewiring.

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Coordinator

DEUTSCHES ZENTRUM FUR NEURODEGENERATIVE ERKRANKUNGEN EV
Net EU contribution
€ 1 687 476,00
Address
Venusberg-campus 1/99
53127 Bonn
Germany

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Region
Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt
Activity type
Research Organisations
Links
Other funding
€ 0,00

Beneficiaries (1)