Astrocytic Ca2+ prevents synaptic depotentiation by limiting repetitive activity in dendrites during motor learning.

Abstract

Astrocytic Ca2+ activity regulates activity-dependent synaptic plasticity, but its role in learning-related synaptic changes in the living brain remains unclear. We found that motor training induced synaptic potentiation on apical dendrites of layer 5 pyramidal neurons, as well as astrocytic Ca2+ rises in the mouse motor cortex. Reducing astrocytic Ca2+ 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 Ca2+ activity. On those dendrites, dendritic spines that were active before dendritic Ca2+ activity underwent CaMKII-dependent size reduction. In addition, the activation of adenosine receptors prevented repetitive dendritic Ca2+ activity and synaptic depotentiation caused by the reduction of astrocytic Ca2+, suggesting the involvement of ATP released from astrocytes and adenosine signaling in the processes. Together, these findings reveal the function of astrocytic Ca2+ in preventing synaptic depotentiation by limiting repetitive dendritic activity during learning.