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Institute of Neurology
Principles of synaptic signal formation in the brain
We are interested in molecular and biophysical mechanisms that control formation and use-dependent modification of rapid transmission signals generated at individual central synapses. We focus on (a) events inside the synaptic cleft, (b) receptor control of presynaptic Ca2+ dynamics, (c) the surrounding glia. To probe these mechanisms, we combine patch-clamp electrophysiology, two-photon excitation imaging, photolytic uncaging and life-time fluorescence microscopy in ex-vivo brain preparations with biophysical modelling.
Current projects include: investigating the role of receptor co-agonists released by astrocytes in use-dependent synaptic plasticity; examining the mechanisms which determine the content of glutamate-filled synaptic vesicles; studying initiation and propagation of action potentials in mossy fibre circuitry of the hippocampus; examining the role of electric fields in shaping neurotransmitter diffusion in the synaptic cleft.
ADDITIONAL INFO: http://www.ion.ucl.ac.uk/~drusakov/
Possible 3-month projects:
1. Ca2+ nano-domains and interpretation of fluorescence Ca2+ imaging at individual presynaptic terminals. Methods: biophysical modelling.
2. Mapping nano-scale extracellular viscosity in the brain. Methods: Acute slices, two-photon time-resolved fluorescence anisotropy imaging microscopy.
3. Axonal Na+ kinetics in mossy fibre circuitry. Methods: patch-clamp electrophysiology, two-photon excitation microscopy.
Henneberger C, Papouin T, Oliet SHR, Rusakov DA (2010) Long-term potentiation depends on release of D-serine from astrocytes. Nature 463: 232-236 (News and Views, 169-170).
Sylantyev S, Savtchenko LP, Niu Y-P, Ivanov AI, Jensen TP, Kullmann DM, Xiao MY, Rusakov DA (2008) Electric fields due to synaptic currents sharpen excitatory transmission. Science 319: 1845-1849.
Savtchenko LP, Rusakov DA (2007) The optimal height of the synaptic cleft. PNAS USA 104: 1823-1828.
Lamsa KP, Heeroma JH, Somogyi P, Rusakov DA, Kullmann DM (2007) Anti-Hebbian long-term potentiation in the hippocampal feedback inhibitory circuit. Science 315: 1262-1266.
Volynski KE, Rusakov DA, Kullmann DM (2006) Presynaptic fluctuations and release-independent depression. Nature Neurosci 9: 1091-1093.
Rusakov DA, Fine A (2003) Extracellular Ca2+ depletion contributes to fast activity-dependent modulation of synaptic transmission in the brain. Neuron 37: 287-297.