Oligodendrocyte progenitor cells: role and function in the healthy and injured brain
Abstract: The idea that NG2-glia and myelin can also influence diseases mainly associated with neurons has emerged in the last years. Here, I am going to introduce NG2-glia and their role in health, injury and disease and show an example of a neuronal disease with a synaptic phenotype where glia and myelination are also affected and can even cause at least part of the pathology. 
Phelan-Mc-Dermid syndrome (PMDS) is a subtype of Autism Spectrum Disorders (ASDs), which is caused by mutations or deletion of the postsynaptic scaffold protein SHANK3, leading to synaptic deficits. PMDS-patients show alterations in the white matter tracts and we could recently identify various myelin defects in SHANK3 deficient mice. As synaptic connections also occur between neurons and NG2-glia, we aimed to study whether these myelin abnormalities could be due to a disruption in this synaptic communication. Indeed, deletion of SHANK3 specifically in NG2-glia affects their proliferation and differentiation and leads to motor and behavioural abnormalities. 
Using this novel mouse model, we reveal new insights into the role of NG2-glia in ASDs as well as into the physiological function of neuron-NG2-glia synapses in the adult CNS. These results show an early and strong involvement of oligodendrocytes and myelin in neurological/-psychiatric diseases that were thought to be fully neuronal and open new avenues for the development of therapeutic strategies this time targeting glia.

The role of microglia in Aβ propagation
Abstract: The aggregation of Aβ is an essential early trigger in Alzheimer’s disease (AD) pathogenesis that leads to neurofibrillary tangles, neuronal dysfunction and dementia. Several cell types have been proposed to be causally involved in amyloid plaque formation, including microglia, owing to their close association with Aβ plaques. As soon as Aβ plaques form in the brain, microglia establish an intimate contact with them and become reactive. Those activated microglia have been linked to plaque growth by Aβ uptake followed by microglial cell death. Our group and others have recently implicated microglia in Aβ seeding and at later stages in compacting amyloid plaques, yet their role in propagating Aβ pathology remains elusive. The fact that microglia are phagocytic cells prompted us to speculate that Aβ can be transported by microglia. By using neural grafting experiments we could show that the formation of Aβ plaques in grafted, unaffected tissue depend on the host microglia functionality. Targeting microglia function might therefore provide an opportunity to interfere with the propagation of Aβ.

Large-scale brain architecture in disease: lessons from acute and chronic damage
Abstract: The wiring of the brain is determined during development but continue to evolve in the adulthood and does respond to disease in peculiar ways. The structure of the brain circuits upon neurodegeneration or neurotrauma constitutes the link between clinical manifestations and personal perspectives one one side and cellular and molecular events on the other side. We employ adeno-associated virus and rabies virus tracing systems to detail mesoscale (area to area) and single-cell resolution circuits in murine models of brain disorders. We have uncovered increases and decreases in connectivity taking place in motoneuron diseases, which changes affecting not only the primary motor cortex but also the connections between cortex and hypothalamus. Furthermore, we have used the cell-resolved connectome of distinct hypothalamic cells to identify new vulnerable subpopularions. Finally, we have traced the recovery of the connectome upon acute injury. These datasets contribute to interpret how the structure of the brain gives raise to the clinical manifestations of disease and to the subjective symptoms experienced by patients.