Age-related differences in behavior-driven activity in LEC but not MEC

The hippocampus integrates spatial information from medial entorhinal cortex (MEC) with non-spatial sensory information from lateral entorhinal cortex (LEC) to form episodic memories. While age-related memory dysfunction is linked to several changes in neuronal function within hippocampal subfields, the effects of aging on MEC and LEC cellular activity patterns are less well-characterized. Here, we investigated MEC and LEC population activity in adult versus aged rats by monitoring the expression of the immediate early gene Arc across two behavioral task sessions with olfactory stimuli separated by a rest period. Aging did not affect the percentage of activated neurons in MEC or their consistent Arc expression patterns across sessions, consistent with stably coding repeated spatial experiences. In contrast, fewer LEC neurons were activated during behavior in aged than adult rats, indicating a specific age-associated hypoactivity in LEC. Additionally, regardless of group, more LEC neurons were activated during the second session compared to the first, which may reflect temporally sensitive LEC neuronal activity increasingly engaged across episodes of experience. These results indicate that aging affects input to the hippocampus in a region-specific manner and are also consistent with observations that suggest that some LEC neurons may provide a temporal tag for episodic memories.