Neurofilaments, neuron-specific cytoskeletal proteins, are heteropolymers composed of four subunits: NFL, NFM, NFH, and αINTX. The synaptic population (SNFs) differs from the axonal subgroup and subserves unique functions, such as the maintenance of synaptic integrity and the modulation of neurotransmission. During aging, synapses undergo several modifications, contributing to the worsening of cognitive performances and the so-called age-related memory impairment. Despite that, nothing is known about "senescent" SNFs. Our research aimed to study the age-related expression pattern of SNFs subunits, whether those changes influence cognitive performances, and whether environmental enrichment (EE) can modulate them. Western blot analysis showed significant differences in cortical and hippocampal SNFs levels of adult (A), late adult (LA) and old (O) rats in comparison to young controls (Y). Confocal analysis confirmed these expression changes in specific layers of dentate gyrus, CA3, CA1 and prefrontal cortex, in relation to synaptic markers. SNFs changes of A and LA correlated to spatial learning and memory evaluated by the Morris Water Maze test. Enriched A and LA showed SNFs values comparable to those of Y. These results suggest that the modified expression pattern of SNFs subunits influences cognitive performances during aging and that EE may be used as a preventive approach to maintain a more functional arrangement. Thus, these preliminary findings highlight that SNFs could be a novel therapeutic target to preserve brain function or to slow down its weakening during aging.