Fig. 1.

Astrocyte‐derived IL‐33 regulates homeostatic synaptic plasticity at hippocampal CA3–CA1 excitatory synapses in a negative feedback manner. In response to the inhibition of hippocampal neuronal activity (1), astrocytes in the CA1 stratum radiatum region undergo transcriptional reprogramming to increase IL‐33 expression (2). The synthesized IL‐33 is then secreted from astrocytes (3) and binds to the neuronal postsynaptic receptor complex ST2/IL‐1RAcP (4), which further promotes the synaptic accumulation of PSD‐95 as well as subsequent synaptogenesis in CA1 pyramidal neurons (5). AMPAR, AMPA receptor; CA, cornu ammonis; DG,dentate gyrus; EAAT, excitatory amino acid transporter; NMDAR, NMDA receptor.