Dissecting neuronal-glial cross-talk via an inducible neuronal silencing tool

Two types of brain cells are mainly involved in how our brain works, the nerve cell and the glial cell. Modern neuroimaging technology has revolutionized our knowledge on the function of astrocytes, the predominant glial cell type in the brain. In our study, we look at mechanisms by which glial cells and nerve cells communicate. Using cutting-edge imaging technology, two-photon microscopy imaging, method and genetically encoded probes, we observed activities in these two types of cells in the mouse brain of awake and behaving mice under behaviour tasks. We found that the astrocytes are able to be activated by both local neuronal network and other centralized neuromodulatory systems.

1) The project has facilitated the applicant's international collaboration network, and also built up her own research team. She established her own research group and moved from UiO to NTNU. The research direction has been guided and supported from this RCN project. The glia research from the group has been also popularised to both her international collaboration network as well as national network. And the results and publications from the project/applicant is leading the current research field. 2) The establishment national platform (NORBRAIN: a Large-scale Infrastructure for 21st Century Neuroscience) combined with applicants competence in molecular tools engineering and two-photon microscopy in awake behaving animals has benefit of numerous investigators using this national infrastructure.

Accumulating evidence in the recent decade indicates that the fore long neglected glial cells are tightly engaged in brain network function. However, up to now, it is not established how glial activities are modulating neuronal circuit function, especially the field of neuronal-glial communication in awake behaving animals remains unexplored. The lack of tools has hampered progress in glial research. In the present project applied, the applicant aims at developing novel molecular approaches for glial research. The overall objective is to dissect the precise mechanisms by which glia and neurons communicate. Ivermectin (IVM) inducible neuronal silencing, a novel strategy for regional and cell type specific inhibition of neurons, will be used to dissect glial activities contributing to neuronal circuits. The project also utilizes virally delivered genetically encoded fluorescent sensors of various molecules in combination with two-photon microscopy of head-fixed awake mice under behavior tasks. The unique combination of cutting-edge approaches - the two-photon imaging in head-fixed behaving mice, genetically encoded sensors and the IVM inducible neuronal silencing - will bring the glial research to a new level. If funded, this project will open up a new page of research on neuronal-glial cross-talk to gain a more comprehensive understanding of the workings of the brain.