Reduction in the activity of VTA/SNc dopaminergic neurons underlies aging-related decline in novelty seeking

Curiosity, or novelty seeking, is a fundamental mechanism motivating animals to explore and exploit environments to improve survival, and is also positively associated with cognitive, intrapersonal and interpersonal well-being in humans. However, curiosity declines as humans age, and the decline even positively predicts the extent of cognitive decline in Alzheimer's disease patients. Therefore, determining the underlying mechanism, which is currently unknown, is an urgent task for the present aging society that is growing at an unprecedented rate. This study finds that seeking behaviors for both social and inanimate novelties are compromised in aged mice, suggesting that the aging-related decline in curiosity and novelty-seeking is a biological process. This study further identifies an aging-related reduction in the activity (manifesting as a reduction in spontaneous firing) of dopaminergic neurons in the ventral tegmental area (VTA) and substantia nigra pars compacta (SNc). Finally, this study establishes that this reduction in activity causally underlies the aging-related decline in novelty-seeking behaviors. This study potentially provides an interventional strategy for maintaining high curiosity in the aged population, i.e., compensating for the reduced activity of VTA/SNc dopaminergic neurons, enabling the aged population to cope more smoothly with the present growing aging society, physically, cognitively and socioeconomically. Behavioral tests together with specific neuronal recordings and manipulation suggest that aging-related decline in social and inanimate novelty seeking is caused by a reduction in the spontaneous firing of midbrain VTA/SNc dopaminergic neurons.

Automated summary

Curiosity and novelty-seeking are fundamental for animals and humans to explore and adapt to their environment, but these traits decline with age in humans and can even predict cognitive decline in Alzheimer's disease. This study shows that aged mice exhibit compromised seeking behaviors for both social and inanimate novelties, suggesting a biological process behind the aging-related decline in curiosity. The study also identifies a reduction in the activity of dopaminergic neurons in specific brain regions as causally related to the decline in novelty-seeking behaviors. These findings could provide intervention strategies to maintain curiosity in the aging population.