Spatial memory deficit across aging: current insights of the role of 5-HT(7) receptors

Elderly persons often face biological, psychological or social changes over time that may cause discomfort or morbidity. While some cognitive domains remain stable over time, others undergo a decline. Spatial navigation is a complex cognitive function essential for independence, safety and quality of life. While egocentric (body-centered) navigation is quite preserved during aging, allocentric (externally-centered) navigation—based on a cognitive map using distant landmarks—declines with age. Recent preclinical studies showed that serotonergic 5-HT(7) receptors are localized in brain regions associated with allocentric spatial navigation processing. Behavioral assessments with pharmacological or genetic tools have confirmed the role of 5-HT(7) receptors in allocentric navigation. Moreover, few data suggested a selective age-related decrease in the expression of 5-HT(7) receptors in pivotal brain structures implicated in allocentric navigation such as the hippocampal CA3 region. We aim to provide a short overview of the potential role of 5-HT(7) receptors in spatial navigation, and to argue for their interests as therapeutic targets against age-related cognitive decline.