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Involvement of a lateral entorhinal cortex engram in episodic-like memory recall

Highlights
• A specific LEC activation is induced by episodic-like memory processing
• Episodic-like memory expression correlates with LEC synaptic plasticity changes
• Inhibition of LEC learning-tagged neurons impairs episodic-like memory recall
• Reactivation of LEC engrams is crucial for episodic-like memory recall


Summary
 Episodic memory relies on the entorhinal cortex (EC), a crucial hub connecting the hippocampus and sensory processing regions. This study investigates the role of the lateral EC (LEC) in episodic-like memory in mice. Here, we employ the object-place-context-recognition task (OPCRT), a behavioral test used to study episodic-like memory in rodents. Electrophysiology in brain slices reveals that OPCRT specifically induces a shift in the threshold for the induction of synaptic plasticity in LEC superficial layer II. Additionally, a dual viral system is used to express chemogenetic receptors coupled to the c-Fos promoter in neurons recruited during the learning. We demonstrate that the inhibition of LEC neurons impairs the performance of the mice in the memory task, while their stimulation significantly facilitates memory recall. Our findings provide evidence for an episodic-like memory engram in the LEC and emphasize its role in memory processing within the broader network of episodic memory.