• Spatial range of neurotransmitter action

    The central nervous system is a highly organized system in which millions of neurons communicate using diffusible transmitters at synaptic connections. Powerful transmitter uptake and diffusional dilution principally limit the spread of transmitter to neighbouring synapses and permit a point-to-point communication between two individual neurons despite an extremely high density of synapses in the neuropil. However, activation of high affinity receptors by transmitter from remote sources may also play important roles in the activity of synaptic micro-networks. These remote sources can influence synaptic plasticity, presynaptic release probability and postsynaptic excitability. Understanding remote neurotransmitter actions will be highly relevant for our understanding of synaptic integration and network excitability.

  • Synaptic integration by NG2 glial cells

    NG2 expressing oligodendrocyte precursor cells stand out from other types of glial cells by receiving classical synaptic contacts from many neurons. This unconventional form of signalling between neurons and glial cells enables NG2 cells to receive information about the activity of presynaptic neurons with high temporal and spatial precision and has been postulated to be involved in activity-dependent myelination. While this still unproven concept generally is compelling, the way how NG2 cells may integrate synaptic input has hardly been addressed to date. In this project we explore the capabilities of NG2 cells to perform complex temporal and spatial signal integration.

    Read about our view of NG2 cells

  • Immobile calcium buffers tune local calcium availability

    We isolated the fixed buffer fraction by prolonged whole-cell patch clamp dialysis and quantified its buffering capacity in murine hippocampal slices using confocal calcium imaging and the "added-buffer" approach.
    A large fixed buffer capacity strongly delays the spread of calcium in granule cells, but it optimizes the benefits of additionally expressing the mobile calcium binding protein calbindin. The data suggests that the amount of fixed buffers determines the temporal availability of calcium for calcium-binding partners and plays a pivotal role in setting the repertoire of cellular calcium signalling regimes.

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  • The Fate of Synaptic Input to NG2 Cells

    Every NG2 cell receives synaptic input from many axons but it is unclear whether neurons specifically synapse onto OPCs or whether OPCs merely trace adjacent neurotransmitter release sites. With whole-cell recordings from distinct developmental stages of oligodendroglial cells we show that synaptic input essentially disappears as soon as OPCs differentiate into premyelinating oligodendrocytes. Premyelinating oligodendrocytes still express a AMPA/kainate receptors and many processes, but spontaneous and stimulated synaptic currents are mostly absent. Nevertheless, in a minority of premyelinating cells, electrical stimulation evoked small synaptic currents with an unusual behavior: they occurred asynchronously and with the remarkable latency of 40 –100 ms, indicating that the presynaptic release machinery has become ineffective. This paper shows that neurons selectively synapse onto only one developmental stage of glial cells and thereby indicates that neurons indeed specifically signal to OPCs and are able to modulate transmitter output by regulating the local release machinery in a manner specific to the developmental stage of the postsynaptic glial cell.

  • Modulating glutamate release probability downstream of presynaptic Calcium entry

    The ubiquitous presynaptic metabotropic glutamate receptors (mGluRs) are generally believed to primarily inhibit synaptic transmission through blockade of Calcium entry. We analyzed how mGluR8 achieves a nearly complete inhibition of glutamate release at hippocampal synapses. Surprisingly, our data suggest that the inhibition produced by mGluR8 may be explained by a decrease in the apparent Calcium affinity of the release sensor and, to a smaller extent, by a reduction of the maximal release rate. Our data identify a mode of presynaptic inhibition which allows mGluR8 to profoundly inhibit vesicle fusion while not diminishing vesicle replenishment.

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