Long-term olfactory enrichment broadly improves cognition in older mice.

Long-term olfactory enrichment induces local expansion of noradrenergic innervation.

Long-term olfactory enrichment drives task-specific brain network remodeling.

Olfactory stimulation along the life span allows the cognitive reserve build up.

Brain functional and structural changes lead to cognitive decline during aging, but a high level of cognitive stimulation during life can improve cognitive performances in the older adults, forming the cognitive reserve. Noradrenaline has been proposed as a molecular link between environmental stimulation and constitution of the cognitive reserve. Taking advantage of the ability of olfactory stimulation to activate noradrenergic neurons of the locus coeruleus, we used repeated olfactory enrichment sessions over the mouse lifespan to enable the cognitive reserve buildup. Mice submitted to olfactory enrichment, whether started in early or late adulthood, displayed improved olfactory discrimination at late ages and interestingly, improved spatial memory and cognitive flexibility. Moreover, olfactory and non-olfactory cognitive performances correlated with increased noradrenergic innervation in the olfactory bulb and dorsal hippocampus. Finally, c-Fos mapping and connectivity analysis revealed task-specific remodeling of functional neural networks in enriched older mice. Long-term olfactory enrichment thus triggers structural noradrenergic plasticity and network remodeling associated with better cognitive aging and thereby forms a promising mouse model of the cognitive reserve buildup.

Noradrenaline

Brain aging

Odors

Mouse

Cognitive reserve

Memory

Cognitive

Flexibility

Functional Connectivity

Remediation

© 2024 The Authors. Published by Elsevier Inc.