Growth hormone is required for hippocampal engram cell maturation

Memory is thought to be stored in a sparse population of neurons or synapses ¹ . These neurons or synapses collectively termed the engram are necessary and sufficient for memory recall ^2,3 . Learning induces synaptic strengthening in engram cells at both pre- and postsynaptic sites ^4,5 . However, the critical time window and the molecule related to the induction of such synaptic changes are unknown. Here we show that the initial translation plays a key role in engram maturation by facilitating pre- and postsynaptic strengthening and that growth hormone (GH) is required to induce this process in the Dentate Gyrus. Using anisomycin, a protein synthesis inhibitor, we found that blocking the initial and the subsequent second wave of translation arrests the maturation of engram cells. Revisiting our hippocampal translatome during memory formation ⁶ proposed GH as a mediator of engram maturation. Overexpression of the dominant negative (G118R) GH blocked the maturation of the hippocampal engram cell ⁷ . Facilitating activity-dependent GH uptake by injecting recombinant human GH (rhGH) into the animal rescued the arrestment caused by anisomycin. Together, our findings propose GH as a key mediator of hippocampal engram cell maturation.