Microglia are the mononuclear phagocytes in the central nervous system. They are critical regulators of inflammation and immunity and their dysfunction has been linked to a wide range of diseases. Microglia are also emerging as important regulators of normal brain physiology. However, the extent of microglial involvement in shaping neuronal circuits remains unclear, as are the molecular mechanisms. One obstacle has been the difficulty to genetically target microglia or to create microglia-deficient mice. Here we propose to generate a new genetic strategy to uniquely target microglia in vivo. This includes the induction of microglial deficiency or microglial activation during any chosen developmental stage. In addition, we will be able to induce conditional gene deletions in microglia, without affecting other immune cells. After genetically targeting microglia, either at embryonic or adult stages, we will assess the consequences on the development and functions of neural circuits and on learning and memory, using olfaction-based anatomical, functional and behavioural paradigms. Besides evaluating the roles of microglia under homeostatic conditions, we will also assess the consequences of microglial deficiency in the restoration of neural circuits following induced neuronal cell death and deafferentation. This work may lead to important new insights in the biology of microglia and will introduce new genetic strategies and tools for the study of mononuclear phagocytes.
|Effective start/end date||1/01/16 → 31/12/16|
Flemish discipline codes
- Systems biology not elsewhere classified
- Laboratory medicine