Alterations in astrocyte calcium signaling have been associated with synaptic dysfunction in Alzheimer’s disease (AD). However, its role in regulating synaptic changes during the learning process in the living brain remains largely unexplored. Utilizing longitudinal, high-resolution imaging of astrocytes and dendritic spines, we found that in control mice motor training induced synaptic potentiation on apical dendrites of layer 5 pyramidal neurons, as well as a substantial rise in calcium within the processes and somas of astrocytes in the superficial layer of the mouse motor cortex. When motor training-triggered astrocytic calcium was reduced either by suppressing α1 adrenergic receptor-IP₃R2 signaling or activating Gq-DREADD receptors in astrocytes, it led to synaptic depotentiation during motor training and subsequent impairment in performance improvement. Notably, synaptic depotentiation occurred on a fraction of dendrites with repetitive dendritic calcium activity. On those dendrites, dendritic spines that were active prior to dendritic calcium activity underwent CaMKII-dependent size reduction during motor learning. In addition, the activation of adenosine receptors prevented repetitive dendritic calcium activity and synaptic depotentiation caused by the reduction of astrocytic calcium, suggesting the involvement of ATP released from astrocytes and adenosine signaling in the processes. Together, our findings suggest a potential mechanism of astrocytic calcium in preventing synaptic dysfunction during learning in AD condition.