Fear-triggered reactive astrocytes orchestrate selective aversive memory decay via IL-3–CSF2RB2 signaling

Forgetting is a fundamental component of the memory system. While existing studies have primarily explored global neural network underlying active forgetting1, the intrinsic pathways impeding selective long-term memory stability remain elusive. Contemporary research has identified multiple decay mechanisms—including adult hippocampal neurogenesis2-6, microglia complement-mediated synaptic pruning7, 8, and protein degradation pathways9-13, yet these predominantly facilitate broad, nonspecific remodeling of neural networks. Whether dedicated mechanisms exist to achieve selective memory decay remains a fundamental unresolved question. Here, we identify a specialized subpopulation of astrocytes, termed Fear-Triggered Reactive Astrocytes (FTRA) in the hippocampal dentate gyrus, which are activated gradually but selectively after contextual fear memory. The FTRA serves as a chronic reducer of fear memory through uniquely release of interleukin-3 (IL-3) and its receptor CSF2RB2 mediated GPCR signaling and mitochondrial‑related energy metabolism in mossy cells. This leads to attenuated mossy cell excitability and behavior-associated calcium signals in granular cell neurons, ultimately driving memory loss. The FTRA operates independently of neurogenesis or microglial pruning, revealing IL-3 as a specific cytokine for spontaneous forgetting and establishing astrocytes as negative mediator of aversive memory maintenance.