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Dmitri Rusakov"Environmental control of transmission at individual hippocampal synapses"

Abstract :

Synaptic microenvironment and its use-dependent modifications shape neurotransmitter signalling in central circuits. Here I will focus on three different aspects of the environment-function relationship at hippocampal synapses.
Firstly, we ask whether the reported long-range electrotonic control of neurotransmitter release at mossy fibre - CA3 pyramidal cell synapses involves changes in presynaptic Ca2+. We combine two-photon excitation Ca2+ imaging with dual-patch recordings from granule cell somata and axonal boutons to show that presynaptic depolarization sufficient to enhance glutamate release has no effect on either basal or action potential-evoked presynaptic Ca2+ signals. Secondly, we ask whether the instantaneous mobility of neurotransmitters (or other small molecules) in the brain extracellular space is as fast as in a free medium. To address this, we apply time-resolved fluorescence anisotropy imaging and use two-photon excitation of a small cell-impermeable probe in hippocampal slices to find that instantaneous extracellular diffusion is 25-30% slower than in a physiological solution. This retardation factor provides a basic constraint for diffusion-limited reactions and molecular mobility in the brain extracellular space. Finally, we ask whether the uneven glial coverage of synapses reflects their functional modality. We reconstruct and quantify 3D ultrastructure of neuropil fragments in the dentate gyrus to find that astroglia approach synapses on ‘thin’ dendritic spines substantially closer than those on ‘mushroom spines’. This distinction suggests that diffusion-dependent synapse-glia communication near 'learning' synapses on thin spines (equipped predominantly with NMDA receptors) could be stronger than that near 'more mature' synapses on larger spines. 

Selected publications

Sylantyev,S., Savtchenko,L.P., Niu,Y.P., Ivanov,A.I., Jensen,T.P., Kullmann,D.M., Xiao,M.Y., Rusakov,D.A. (2008). Electric fields due to synaptic currents sharpen excitatory transmission. Science 319(5871), 1845-1849.
Lamsa,K.P., Heeroma,J.H., Somogyi,P., Rusakov,D.A., Kullmann,D.M. (2007). Anti-Hebbian long-term potentiation in the hippocampal feedback inhibitory circuit. Science 315(5816), 1262-1266.
Savtchenko,L.P., Rusakov,D.A. (2007). The optimal height of the synaptic cleft. Proceedings of the National Academy of Sciences of the United States of America 104(6), 1823-1828.

Stéphane Oliet