Growth hormone is required for hippocampal engram cell maturation

Abstract

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.