Cholinergic transmission is fundamental in memory mechanisms. Accordingly, the early degeneration of cholinergic fibers characterizing Alzheimer’s disease (AD) contributes to cognitive impairment, and mice lacking functional α7 nicotinic acetylcholine receptors (A7KO) develop an age-dependent AD-like phenotype, featuring increased levels of β-amyloid and phospho-tau, hippocampal plasticity deficits, neuronal loss and astrogliosis. Astrocytes, recognized partners of neurons in brain function, are characterized by a signaling system based on variations in intracellular Ca2+ concentration. Experimental evidences from different AD mouse models suggest that astrocyte signal alterations are involved in AD pathogenesis. Our project aims to characterize astrocytes from A7KO mice, to unravel the role of A7 receptor in astrocytic calcium modulation and disclose possible astrocyte contributions to AD-like phenotype. We also analyze how calcium signal in hippocampal astrocytes is affected by aging and by the presence of β-amyloid oligomers. Spontaneous and metabotropic agonist-evoked Ca2+ signals are monitored at soma and branches (down to thin microdomains) of GCaMP6-expressing hippocampal astrocytes from young (4mo) and middle-aged (12mo) WT and A7KO mice. Results obtained in WT mice show that while spontaneous and evoked somatic activity are maintained along aging, a significant reduction in signal frequency is observed at astrocyte thin processes. Preliminary results also suggest that Ca2+ microdomains can be acutely activated by β-amyloid oligomers. Our data thus reveal that microdomain signaling sites are preferentially affected by both aging and β-amyloid. We are currently performing experiments on A7KO mice, to disclose whether microdomain activity is differentially shaped in the absence of functional A7 receptors.