Engram Cell Excitability State Determines the Efficacy of Memory Retrieval

Animals need to optimize the efficacy of memory retrieval to adapt to environmental circumstances for survival. The recent development of memory engram labeling technology allows a precise investigation of the processes associated with the recall of a specific memory. Here, we show that engram cell excitability is transiently increased following memory reactivation. This short-term increase of engram excitability enhances the subsequent retrieval of specific memory content in response to cues and is manifest in the animal’s ability to recognize contexts more precisely and more effectively. These results reveal a hitherto unknown transient enhancement of context recognition based on the plasticity of engram cell excitability. They also suggest that recall of a contextual memory is influenced by previous but recent activation of the same engram. The state of excitability of engram cells mediates differential behavioral outcomes upon memory retrieval and may be crucial for survival by promoting adaptive behavior. •Memory recall induces a transient increase in engram cell excitability•The engram excitability increase is mediated by Kir2.1 channel internalization•The engram high-excitability state is associated with enhanced context recognition•Engram-specific exogenous expression of Kir2.1 channels impairs context recognition Memory exists across different time scales. Long-term memories can last a lifetime, while working memory persists for mere seconds. In between, memories that are newly formed—or recently recalled—are more vivid than latent ones. How does this happen? The act of memory recall increases the excitability of whole engram cells for about one hour. This short-term increase of engram cell excitability facilitates synaptic access to memory content in response to relevant environmental cues.