Abstract

Experience-dependent plasticity of synaptic transmission, which represents the cellular basis of learning, is accompanied by morphological changes in dendritic spines. Astrocytic processes are intimately associated with synapses, structurally enwrapping and functionally interacting with dendritic spines and synaptic terminals by responding to neurotransmitters and by releasing gliotransmitters that regulate synaptic function. While studies on structural synaptic plasticity have focused on neuronal elements, the structural–functional plasticity of astrocyte–neuron relationships remains poorly known. Here we show that stimuli inducing hippocampal synaptic LTP enhance the motility of synapse-associated astrocytic processes. This motility increase is relatively rapid, starting <5 min after the stimulus, and reaching a maximum in 20–30 min (t(1/2) = 10.7 min). It depends on presynaptic activity and requires G-protein-mediated Ca2+ elevations in astrocytes. The structural remodeling is accompanied by changes in the ability of astrocytes to regulate synaptic transmission. Sensory stimuli that increase astrocyte Ca2+ also induce similar plasticity in mouse somatosensory cortex in vivo. Therefore, structural relationships between astrocytic processes and dendritic spines undergo activity-dependent changes with metaplasticity consequences on synaptic regulation. These results reveal novel forms of synaptic plasticity based on structural–functional changes of astrocyte–neuron interactions.