Our research focuses primarily on how glial cells and neurons interact to maintain normal brain function and long-term cellular integrity. The importance of glial cells in regulating neuronal activity and brain energy homeostasis is not fully understood. The current working model suggests that both myelinating oligodendrocytes and astrocytes, which form a pan-glial syncytium by gap-junction coupling, are highly glycolytic and supply neuronal compartments with energy substrates to fuel energy demands and to support long-term integrity. However, what are the cellular mechanisms regulating such neuron-glial interactions and metabolic cooperation? And could perturbations in neuron-glial communication and deficits in glial metabolic support impact the etiology and pathogenesis of age-related neuropsychiatric and degenerative diseases, e.g. Alzheimer’s disease? How do myelinating oligodendrocytes and astrocytes sense neuronal activity and how are these signals translated into maintaining neuronal functions in the young and aging brain? How are these cellular interactions perturbed during normal aging and upon neurological pathologies? To address these questions we combine molecular genetics, electrophysiology, in vivo and ex vivo two-photon imaging, histology, electron microscopy and behavioral studies in mice to investigate cellular mechanisms regulating intercellular communication, brain energy homeostasis and cellular integrity.