February 10, 2011 16:00 - 17:00
A growing body of experimental evidence suggests that Ca2+ signals in astroglia can trigger release of important signalling molecules ('gliotransmitters') into the brain extracellular space. Whether such release directly affects synaptic function remains a subject of intense debates. We have found that clamping internal Ca2+ in individual hippocampal astrocytes in situ blocks induction of long-term potentiation (LTP) at nearby, but not remote, CA3-CA1 excitatory synapses, by reducing the occupancy of the local NMDA receptor co-agonist binding sites. Synaptic plasticity can be restored exogenously by the NMDA receptor co-agonists D-serine or glycine whereas metabolic depletion of D-serine or disruption of exocytosis inside an individual astrocyte reproduces the synaptic memory blockade (Nature 2010, 463: 232). Induction of LTP is paralleled by subtle changes in astrocytic morphology monitored in real-time with two-photon excitation imaging methods developed ad hoc. On the synaptic level, these changes are reflected in the glial coverage of synapses assessed with 3D electron microscopy of individually labelled astrocytes. To understand the underlying Ca2+-dependent mechanisms, we currently investigate Ca2+ signalling inside astrocytes using a system of fluorescence life-time imaging (FLIM) coupled with patch-clamp electrophysiology and two-photon excitation.
- BSI Private Event
- Alexey Semyanov