Neuron-glial communication in the Central Nervous System is fundamentally important for many brain processes including synaptic transmission and plasticity. Intracellular calcium signaling appears to be a key event occurring in astrocytes, a subtype of glial cells, during their interactions with neurons. Astrocytes extend fine processes to enwrap synapses and form tripartite complexes with neuronal synaptic structures. The morphology of both neuronal and glial processes shows rapid and continuous structural remodeling in the hippocampus. These physical modifications are likely to have a significant functional impact upon neurotransmission and suggest that the remodeling of astrocytic morphology might be crucial for the dynamic regulation of the synapse and its microenvironment. Here, we will determine how neuronal activity regulates the morphological interplay between astrocytic processes and synapses. We will also investigate a new role for the astrocytic calcium excitability in controlling astrocytic process motility. In situ studies on neuron-glia interactions are technically challenging due to the difficulty of obtaining cell specificity and accurately reproducing the complex calcium excitability of astrocytes. To overcome those difficulties, new tools and approaches are needed. The present proposal will transfer novel strategies based on molecular tools, which have been recently developed by the applicant in his present position at the third country, into the host institution. The applicant will bring his knowledge on glia into a host laboratory with expertise in the field of neuronal synaptic morphology and plasticity. We believe that a novel experimental approach will allow answering previously inaccessible questions and help elucidate the role of neuron-astrocyte morphological interactions in regulating synapses that may be important for understanding synaptic physiology, behavior and brain disease.