New Research: Running in Midlife Preserves ‘Old’ Neurons Born in Adulthood

A novel study shows that prolonged running drastically alters the neuron network formed in adult mice at middle age. Significantly, physical exercise amplifies the input from interneurons in the hippocampus to ‘old’ neurons born in adulthood. These interneurons could help decrease hyperactivity in the hippocampus associated with aging, thereby improving memory function. The credit for the illustration goes to Carmen Vivar, Ph.D.

The research uncovers the mechanism by which exercise helps retain memory function during the aging process.

Cognitive functions often decline with aging. The hippocampus and neighboring cortices, critical for learning and memory, are usually the first to be affected. A decrease in hippocampal volume and impaired synaptic connectivity between the hippocampus and the (peri)-entorhinal cortex is associated with cognitive performance deficits.

Growing evidence suggests that physical activity can help mitigate or delay these structural and functional decreases in older people. A fresh study from Florida Atlantic University and CINVESTAV, Mexico City, Mexico, provides a deeper understanding of exercise benefits. This emphasizes the need for adults, especially those in their middle age, to maintain physical activity throughout their lives.

In the study, the researchers studied the impact of long-term running on a network of newly formed hippocampal neurons in middle-aged mice, originally generated in their young adulthood. This research showed that consistent running during middle age keeps the old neurons, born in adulthood, actively connected, which could help prevent or postpone memory loss and neurodegeneration related to aging.

Adult-born neurons are assumed to aid hippocampus-dependent memory function and are deemed temporarily crucial during the ‘critical period’ around three to six weeks of cell age, where they can briefly exhibit increased synaptic plasticity. Despite their presence for many months, it was uncertain whether those born in early adulthood remain integrated into neural networks and whether physical activity in middle age can modify their circuitry.

To tackle these questions, researchers employed a unique rabies virus-based circuit tracing method with a long time gap between the initial labeling of new neurons and the subsequent analysis of their neural circuitry in rodents. More than six months after marking adult-born neurons with a fluorescent reporter vector, they identified and quantified the direct afferent inputs to these neurons within the hippocampus and (sub)cortical areas when the mice were middle-aged.

The study results, published in the journal eNeuro, reveal that long-term running integrates ‘old’ new neurons, born during early adulthood, into a network crucial for maintaining episodic memory encoding during aging.

“Long-term exercise profoundly impacts the aging brain and could help prevent memory function decline related to aging by increasing the survival and altering the network of the adult-born neurons generated during early adulthood, thereby promoting their participation in cognitive processes,” stated Henriette van Praag, Ph.D., the corresponding author, an associate professor of biomedical science in FAU’s Schmidt College of Medicine, and a member of the FAU Stiles-Nicholson Brain Institute.

The study found that long-term running significantly amplified the number of adult-born neurons and boosted the recruitment of presynaptic (sub)-cortical cells to their network.

“Long-term running may improve our ability to differentiate between highly similar events and stimuli, a behavior closely linked to adult neurogenesis, which is among the first to show deficits indicative of age-related memory decline,” said Carmen Vivar, Ph.D., corresponding author, Department of Physiology, Biophysics and Neuroscience, Centro de Investigacion y de Estudios Avanzados del IPN in Mexico.

Memory function decline related to aging is associated with the degradation of synaptic inputs from the perirhinal and entorhinal cortex onto the hippocampus, brain areas that are essential for pattern separation, and contextual and spatial memory.

Van Praag noted, “Our study shows that running significantly increases the back-projection from the dorsal subiculum onto old adult-born granule cells. This connectivity may provide navigation-associated information and mediate the long-term running-induced improvement in spatial memory function.”

The study found that running not only rescued perirhinal connectivity but also expanded and altered the contribution of the entorhinal cortices to the network of old adult-born neurons.

Vivar concluded, “Our research provides insights on how chronic exercise, starting in young adulthood and continuing throughout middle age, helps maintain memory function during aging, emphasizing the significance of incorporating exercise in our daily routines.”

Reference: “Running throughout Middle-Age Keeps Old Adult-Born Neurons Wired” by Carmen Vivar, Ben Peterson, Alejandro Pinto, Emma Janke and Henriette van Praag, 15 May 2023, eNeuro. DOI: 10.1523/ENEURO.0084-23.2023

The co-authors of the study are Ben Peterson, Ph.D., a postdoc at UC Davis currently; Alejandro Pinto from FAU’s Schmidt College of Medicine and Stiles-Nicholson Brain Institute; and Emma Janke, a recent graduate from the University of Pennsylvania.

The research received partial support from the FAU Stiles-Nicholson Brain Institute and the Jupiter Life Sciences Initiative (awarded to van Praag), and the Fondo de Investigación Científica y Desarrollo Tecnológico del Cinvestav (Proyectos SEP-Cinvestav), (awarded to Vivar).

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More about Running and Memory Function

• Florida Atlantic University
• CINVESTAV, Mexico City
• FAU’s Schmidt College of Medicine
• FAU Stiles-Nicholson Brain Institute
• Study in eNeuro journal