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Dmitri Rusakov & Jeffrey Diamond Collaboration

Title: Excitatory transmission and Ca2+ dependent astrocytic signaling

UCL supervisor: Dmitri Rusakov, Ph.D., UCL Institute of Neurology
NIH supervisor: Jeffery Diamond, Ph.D., Synaptic Physiology Section, NINDS

Background

There is a rapidly growing body of evidence suggesting a functional relationship between Ca2+ signals generated in glia (in particular astrocytes) and the functioning of nearby excitatory synapses. Interference with endogenous Ca2+ homeostasis inside individual astrocytes has been shown to affect synaptic transmission and its use-dependent changes in the hippocampus. However, establishing the causal link between source-specific, physiologically relevant intracellular Ca2+ signals, the astrocytic release machinery and the consequent effects on synaptic transmission has proved difficult. Improved methods of Ca2+ monitoring in situ should be essential for resolving the current ambiguity in understanding the underlying Ca2+ signalling cascades.

Methods

Patch-clamp electrophysiology in astrocytes and neurons combined with two-photon excitation imaging and uncaging in acute slices (hippocampus and retina); fluorescence lifetime imaging of Ca2+ signals inside individual neurons and astrocytes; probing intracellular nano-diffusion with time-resolved fluorescence anisotropy imaging; Monte Carlo simulations of molecular mobility and receptor reactions in complex extracellular environment.

Contact details
Dmitri Rusakov, Ph.D. - d.rusakov@ion.ucl.ac.uk,
Jeffery Diamond, Ph.D. - diamondj@ninds.nih.gov