Transl Neurosci 2026 Jan 04;171:20250392. doi: 10.1515/tnsci-2025-0392.

Rodents' episodic-like memory: concepts, ageing, neurodegeneration, future.

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Episodic memory (EM), traditionally defined as the conscious recollection of what, where, and when events occurred, was long considered uniquely human due to its reliance on autonoetic awareness. However, behavioural criteria allow memory assessment based on observable features, enabling the study of EM-related processes in non-human species and leading to the concept of episodic-like memory (ELM) in animal models. We review conceptual advances and methodological challenges in ELM research, focusing on rodent models that provide mechanistic insights into neural circuits and molecular pathways supporting memory formation and persistence. Converging evidence highlights the role of hippocampal-prefrontal networks in integrating spatial, temporal, and emotional dimensions of experience. We also discuss data from our laboratory, which provides evidence for cellular and synaptic mechanisms, such as tagging-and-capture, ensemble allocation, and reactivation, that contribute to memory linking and consolidation in the fear-based ELM paradigm. These findings indicate that novelty-dependent recruitment of neuronal ensembles in the dorsal CA1 is impaired during ageing, leading to deficits in the persistence of weak experiences. Additionally, studies using cholinergic hypofunction models, a hallmark of late-onset Alzheimer's disease (LOAD), reveal severe impairments in object recognition, spatial location, and integrated ELM, partially reversed by pharmacological interventions. Collectively, these data emphasise the translational relevance of ELM paradigms for modelling age-related memory decline and neurodegeneration. We also address open questions regarding neuromodulatory influences, sex differences, and the boundary between normal ageing and LOAD. By integrating conceptual, behavioural, and neurobiological perspectives, ELM approaches provide powerful tools for probing memory dynamics and informing therapeutic strategies.

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