Summary
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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| Web resources: | https://cordis.europa.eu/project/id/865618 |
| Start date: | 01-09-2020 |
| End date: | 31-08-2025 |
| Total budget - Public funding: | 1 687 476,00 Euro - 1 687 476,00 Euro |
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Original description
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.Status
SIGNEDCall topic
ERC-2019-COGUpdate Date
27-04-2024
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