Astrocyte and neuron cooperation in long-term depression

Our understanding of the mechanisms underlying long-term depression (LTD) is largely limited to the roles played by neuronal elements. However, emerging evidence indicates that a previously overlooked synaptic player – the astrocyte – critically contributes to LTD. There is considerable heterogeneity in the mechanisms of astrocyte involvement in LTD, from their role as homeostatic regulators to active signaling elements. Given that astrocytes have been found to be both necessary elements and integral participants in LTD, obtaining a more complete understanding of the mechanisms underlying LTD will require closer consideration of astrocytes in future studies. Activity-dependent long-term changes in synaptic transmission known as synaptic plasticity are fundamental processes in brain function and are recognized as the cellular basis of learning and memory. While the neuronal mechanisms underlying synaptic plasticity have been largely identified, the involvement of astrocytes in these processes has been less recognized. However, astrocytes are emerging as important cells that regulate synaptic function by interacting with neurons at tripartite synapses. In this review, we discuss recent evidence suggesting that astrocytes are necessary elements in long-term synaptic depression (LTD). We highlight the mechanistic heterogeneity of astrocyte contribution to this form of synaptic plasticity and propose that astrocytes are integral participants in LTD. Activity-dependent long-term changes in synaptic transmission known as synaptic plasticity are fundamental processes in brain function and are recognized as the cellular basis of learning and memory. While the neuronal mechanisms underlying synaptic plasticity have been largely identified, the involvement of astrocytes in these processes has been less recognized. However, astrocytes are emerging as important cells that regulate synaptic function by interacting with neurons at tripartite synapses. In this review, we discuss recent evidence suggesting that astrocytes are necessary elements in long-term synaptic depression (LTD). We highlight the mechanistic heterogeneity of astrocyte contribution to this form of synaptic plasticity and propose that astrocytes are integral participants in LTD.