Growth hormone is required for hippocampal engram cell maturation

Memory is stored in specialized cells known as engram cells, but the molecular mechanisms underlying this process remain unclear. We discovered that the initial translation leading to growth hormone (GH) synthesis in engram cells is required for their maturation in the mouse dentate gyrus. Time-course experiments with a translation inhibitor suggested that the key molecule is immediately translated during learning. We identified GH as the crucial factor, specifically translated within the first few minutes of consolidation in engram cells. Blocking GH activity with a dominant-negative (G118R) mutation blocked engram maturation, whereas facilitating activity-dependent GH uptake alleviated engram maturation deficits caused by translation inhibition. Together, our findings propose GH as a key mediator of hippocampal engram cell maturation.