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VIB KU Leuven – Center for Brain & Disease Research

Country: Belgium

VIB KU Leuven – Center for Brain & Disease Research

1 Projects, page 1 of 1
  • Funder: French National Research Agency (ANR) Project Code: ANR-21-MRS1-0002
    Funder Contribution: 28,336 EUR

    The brain is the most complex organ. Each area of the brain is made up of an intricate network of neurons linked together by synapses, points of contact between neurons. The proper functioning of the brain depends on the correct specific connectivity between subtypes of neurons, usually the axon of a presynaptic neuron and the soma, dendrite, or dendritic spine of a postsynaptic neuron. In the mammalian central nervous system, a typical part of the neuropil contains dozens of synapses per µm3 from many different neurons. The majority of central synapses (~80%) are excitatory, using glutamate as a neurotransmitter, while ~10-20% of synapses are inhibitory (using γ-amino butyric acid (GABA) or glycine as a neurotransmitter). The remaining small minority of synapses are modulatory, using for example dopamine, serotonin or norepinephrine. However, within these neurochemical categories, a great diversity results from differences in the size, efficiency and variability of synaptic transmission, as well as their ability to experience plasticity. Such diversity occurs between neuron types but also within single neurons connecting different types of neurons. Synaptic function depends on a wide repertoire of genes that control adhesion between pre- and post-synaptic elements, the release of neurotransmitters from synaptic vesicles, the type and location of post-synaptic receptors, and the signaling complexes leading to plasticity. Ultimately, knowledge of the molecular composition of synapses would allow us to predict their functional diversity. Moreover, this knowledge is necessary to understand the alterations undergone in genetic diseases affecting the brain or to define therapeutic strategies targeting specific neurons. To further understand the diversity of synaptic function and its alterations in disease, it is essential to combine several state-of-the-art methodologies to identify specific types of neurons, their connectivity with other types of neurons and the morphological, molecular and functional properties of their synapses. We propose to train the next generation of scientists in this field by bringing together a consortium of expert groups, either from leading academic institutions or from thriving biotechnology companies, with expertise in one or more methodological approaches needed to address synaptic diversity: labeling and purification of specific synaptosomes for proteomic analysis (DP/EH, JDW), imaging of living cells at synapse level (CC, DP, SH, ZN), role of adhesion proteins in synapse specification (CC, DKB, JDW), electrophysiology (all groups), in particular pre- and post-synaptic elemental records (SH), electron microscopy and array tomography (ZN). We will combine our expertise to address synaptic diversity in the context of specific synapses such as hippocampal and cerebellar mossy fibers (JDW, SH) and cortical excitatory synapses (JDW, DP, SH, ZN, CC), inhibitory synapses (CC, DKB, ZN), dopaminergic synapses (DP/EH, SH). In addition, the field of synapse function and diversity is at the core of current research on brain disorders, many of which have been recognized as alterations in synapse function or "synaptopathies". Training the next generation of scientists in these rapidly evolving fields will be important in developing innovative strategies for the benefit of every European.

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