What does engram encode?: Heterogeneous memory engrams for different aspects of experience

Long-lasting synaptic changes within the neuronal network mediate memory. Neurons bearing such physical traces of memory (memory engram cells) are often equated with neurons expressing immediate early genes (IEGs) during a specific experience. However, past studies observed the expression of different IEGs in non-overlapping neurons or synaptic plasticity in neurons that do not express a particular IEG. Importantly, recent studies revealed that distinct subsets of neurons expressing different IEGs or even IEG negative-(yet active) neurons support different aspects of memory or computation, suggesting a more complex nature of memory engram cells than previously thought. In this short review, we introduce studies revealing such heterogeneous composition of the memory engram and discuss how the memory system benefits from it. •The heterogeneity of IEGs provides insights into how neuronal ensembles encode different aspects of memory.•Hippocampal c-Fos responds to a novel relational aspect of experience, suggesting a unique contribution to episodic memory.•Heterogeneous memory engram cells might reconcile multiple hypotheses of hippocampal role in memory.