Special BMI LNDC SEMINAR // New advances in microglial physiology and clinical relevance
Event details
| Date | 02.02.2017 |
| Hour | 12:15 › 13:15 |
| Speaker | Renaud Jolivet, Nuclear and Corpuscular Physics Department, University of Geneva |
| Location | |
| Category | Conferences - Seminars |
Microglia, the brain’s immune cells, continually extend and retract processes to survey the brain. This surveillance may be needed to prune redundant or damaged synapses during development or pathology, to modulate neuronal activity and to detect pathogenic agents, but its mechanism is obscure. To examine the signalling regulating microglial process movement, we imaged and whole-cell clamped microglia in situ in brain slices and in vivo. Applying ATP led to membrane hyperpolarization mediated by a P2Y12 receptor-linked ion channel that we identify as the anaesthetic-sensitive two-pore domain K+ channel THIK-1, and evoked process outgrowth towards the ATP source. Blocking P2Y12 receptors prevented process outgrowth in response to ATP released by tissue damage but did not affect the membrane potential or surveillance of the brain by microglia. In contrast, blocking tonic activity of THIK-1 with specific K+ channel inhibitors, gene knockout or gaseous anaesthetics, or locally applying high [K+]o solution, depolarised microglia which decreased microglial ramification and inhibited surveillance of the brain. Blocking THIK-1 activity also inhibited interleukin-1ß release evoked by ATP/lipopolysaccharide-evoked microglial activation. Thus, regulation of the microglial membrane potential by THIK-1 channels (which are not expressed by the cultured microglia often used to assess brain immune function) controls immune surveillance of the brain and immune effector release, suggesting that modulation of THIK-1 channels could be used to alter these functions therapeutically. The inhibitory effect of gaseous anaesthetics on THIK-1 implies that brain immune function may be suppressed in clinical situations using these agents.
Practical information
- Informed public
- Free
Organizer
- SV BMI LNDC Host : P. Magistretti