INDIVIDUAL VARIATIONS OF TEMPORAL ASSOCIATION LEARNING AND ENTORHINAL–CA1 COMMUNICATION IN YOUNG AND AGED MICE

Temporal association learning (TAL) is a fundamental aspect of episodic memory that allows linking events separated in time. This process relies on the hippocampus, the entorhinal cortex and their interaction. To investigate how aging affects TAL and synaptic function related to hippocampal-entorhinal communication, we employed trace fear conditioning to auditory stimuli paired with electric foot-shock applied with stimulus-free trace intervals of 20s. Both young (3-5 months) and aged (20-24 months) C57BL/6J mice showed evidence of acquiring the temporal association and, although no robust age-related deficit in overall task performance was observed, displayed substantial individual variability in behaviour and freezing patterns. To characterize plasticity in the temporoammonic (entorhinal-CA1) pathway, extracellular field recordings were performed in acute hippocampal slices with brief trains (5 pulses) of stimulation applied at different frequencies (2, 10, 20, 40, 60 or 100 Hz). Here, significant age-related differences in facilitation emerged at low frequencies, with aging selectively impairing facilitation at theta frequencies. Our findings suggest that healthy aging in mice is accompanied by alterations in entorhinal-CA1 communication, even in the absence of overt behavioural deficits. Impaired theta-range facilitation may contribute to individual variability in TAL and may represent an early circuit-level alteration that precedes, and potentially predicts, the emergence of temporal association deficits. Ongoing work aims to further elucidate the causal relationship between circuit-level changes and behavioural performance.
Supported by the German Research Foundation (362321501/RTG 2413 SynAGE)