Project description
Reciprocal microglia-neuron signalling and brain physiology
According to the neuron-centred brain view, the electrical signalling of neurons defines the information code of the brain, and synapse connectivity determines circuit functions. However, the brain also contains three glial cell types: astrocytes, oligodendrocytes and microglia. Astrocytes and oligodendrocytes have essential functions in the brain. Microglia are brain-resident immune cells, defending against pathogens and providing a housekeeping function as phagocytes. The EU-funded MICRO-COPS project aims to capitalise on the hypothesis that microglia are also involved in the control of neuronal function under normal physiological conditions. The combination of mouse genetics, gene expression analysis and cell biological, electrophysiological and imaging technologies will define the microglia–neuron signalling pathways and the biological consequences of this crosstalk.
Objective
The brain controls all body functions. At the base of this 'catholic' role are the neurons, cells that generate electrical signals, communicate via synapses and form circuits that execute computing tasks and control behaviour. The electrical signalling pattern of neurons is the information code of the brain and the synapse connectivity determines circuit function. This is, in brief, what most textbooks emphasise, but such a neuron-centred brain view is precariously short-sighted.
Apart from neurons, the brain contains three glia cell types (from Greek 'γλία' for 'glue'): astrocytes, oligodendrocytes, and microglia. But far from being mere 'glue', astrocytes and oligodendrocytes have multiple critical functions in the brain, accordingly affect many brain processes - even genuine computing tasks - and have therefore become a major focus of modern neuroscience.
Microglia are the 'odd one out'. They are brain-resident immune cells, act as defence against pathological insults and have a housekeeping function as phagocytes. Aside from these functions, microglia seem to play an as yet unrecognized role by engaging in reciprocal signalling with neurons. It is this Microglia Control of Physiological Brain States we will study in MICRO-COPS, based on the hypothesis that microglia purposively control neuronal function. We will combine mouse genetics with cutting-edge gene expression analysis and cell biological, electrophysiological, and imaging technologies to define the reciprocal microglia-neuron signalling pathways, the signalling molecules involved, the biological consequences for microglia and neurons, and the role of the corresponding signalling processes in synapse physiology, neuronal integration, circuit dynamics, and behaviour. We expect that the mechanistic description of reciprocal microglia-neuron interactions - from synapses to circuits - will establish a new and critically important brain regulatory process and provide key insights into brain pathology.
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Funding Scheme
ERC-SyG - Synergy grantHost institution
80539 Munchen
Germany