Interplay between astrocytic and neuronal networks during virtual navigation in the mouse hippocampus

Encoding of spatial information in hippocapal place cells is believed to contribute to spatial cognition during navigation. Whether the processing of spatial information is exclusively limited to neuronal cells or it involves other cell types, e.g. glial cells, in the brain is currently unknown. In this thesis work, I developed an analysis pipeline to tackle this question using statistical methods and Information Theory approaches. I applied these analytical tools to two experimental data sets in which neuronal place cells in the hippocampus were imaged using two-photon microscopy, while selectively manipulating astrocytic calcium dynamics with pharmacogenetics during virtual navigation. Using custom analytical methods, we observed that pharmacogenetic perturbation of astrocytic calcium dynamics, through clozapine-n-oxyde (CNO) injection, induced a significant increase in neuronal place field and response profile width compared to control conditions. The distributions of neuronal place field and response profile center were also significantly different upon perturbation of astrocytic calcium dynamics compared to control conditions. Moreover, we found contrasting effect of astrocytic calcium dynamics perturbation on neuronal content of spatial information in the two data sets. In the first data set, we found that CNO injection resulted in a significant increase in the average information content in all neurons. In the second data set, we instead found that mutual information values were not significantly different upon CNO application compared to controls. Although the presented results are still preliminary and more experiments and analyses are needed, these findings suggest that astrocytic calcium dynamics may actively control the way hippocampal neuronal networks encode spatial information during virtual navigation. These data thus suggest a complex and tight interplay between neuronal and astrocytic networks during higher cognitive functions.