Full Stage Lay Summary Learning occurs through changing the strength of transmission at the synaptic junctions between nerve cells. We have found that there is an ongoing regulation of synaptic plasticity determined by the degree of nerve cell activity in the network. Using neurophysiological and imaging techniques, we will test the novel hypothesis that a non-neuronal cell type (astrocytes) acts to monitor ongoing nerve cell activity, and uses this information to control future memory-related changes in synaptic transmission. Such regulation may be important for maintaining normal learning and memory, and its impairment may contribute to the pathophysiology and loss of synaptic plasticity in Alzheimer's disease. To test this latter hypothesis, we will investigate whether these regulatory mechanisms are impaired in an animal model of Alzheimer's disease, and whether normal plasticity can be recovered in this model. Understanding these processes may help identify new molecular targets for therapeutic interventions to rescue impaired memory and cognition.