RESILIENCE TO COGNITIVE AGING IS ASSOCIATED WITH RESPONSIVENESS OF DENTATE NEURONS GENERATED THROUGHOUT ADULT LIFE

Abstract

During aging some individuals are resilient to the decline of cognitive functions whereas others are vulnerable. These inter-individual differences in memory abilities have been associated with differences in the rate of hippocampal neurogenesis measured at old age. Whether the maintenance of the functionality of neurons generated throughout adult life is linked to resilience to cognitive aging remains completely unexplored. Using the immediate early gene Zif268, we analysed the activation of dentate granule neurons born in adult (3 month-old), middle-aged (12 month-old) or senescent (18 month-old) rats (n=96) in response to learning when animals reached 21 month-old. The activation of neurons born during the developmental period was also examined. We show that neurons generated 4, 10 or 19 months before learning (and not developmentally born neurons) are activated in senescent rats with good learning abilities. In contrast, aged rats with bad learning abilities do not exhibit an activity-dependent regulation of Zif268. In conclusion, we propose that resilience to cognitive aging is associated to the responsiveness of neurons born during adult-life. These data add to our current knowledge by showing that the aging of memory abilities stems not only from the number but also from the responsiveness of adult-born neurons.