Astrocyte and neuron cooperation in long-term depression

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.The authors would like to thank María José Acuyo Ruiz for assistance with the figures. This work was supported by grants from the Spanish Ministry of Science and Innovation (Ramón y Cajal RYC-2016-20414 and RTI2018-094887-B-I00) and Fondo Europeo de Desarrollo Regional (FEDER) to M.N.; and National Institutes of Health-MH (R01MH119355), National Institutes of Health-NINDS (R01NS097312), and National Institutes of Health-NIDA (R01DA048822) to A.A