The appropriate functioning of the brain requires co-operation between its cellular constituents – neurons and glial cells. While neurons have been widely studied thanks to their electrical excitability, the glial component has been neglected for years. However, recent research has brought surprising results indicating that astrocytes (a type of glia) can actively regulate the structural and physiological properties of synapses. Unfortunately, most of the data regarding astrocyte function originates from ex vivo studies, because the complexity of the nervous system meant it was impossible to study astrocyte function in vivo with the limited technologies available at the time. It is recent advances in imaging, together with the introduction of novel, genetically modified animals, which now allow us to investigate astrocyte-synapse interactions in situ.
In this multidisciplinary project, I will combine state-of-the-art genetic, biochemical and imaging techniques to study the role of astrocytes in mediating dendritic spine plasticity. First, I will develop a method that allows the flexible generation of genetically modified mice showing astrocyte-specific gene targeting. Second, using these mice I will analyze the dynamic relationship between astrocytic processes and dendritic spines in the mouse cortex in vivo, using 2-photon microscopy and a thinned-skull window. In parallel, I will perform an in vitro screen for astrocytic proteins involved in mediating physical contact with the synapse, by using unique subcellular fractionation techniques combined with mass-spectrometry. Finally, identified proteins will be knocked down with silencing RNA to study their role in astrocyte-synapse interactions in situ.
This project will generate fundamental knowledge on how astrocytes influence the structure of neuronal networks in vivo. Such knowledge is essential if we are ever to successfully treat neurological conditions, such as schizophrenia, mental retardation and stroke.
Fields of science
Call for proposal
See other projects for this call