Long Term Exercise Improves Neurogenesis and Memory Function in Mice

Exercise is demonstrated to improve memory function, both immediately in the short-term, and over the long term of regular exercise and improved physical fitness. Exercise is also known to improve measures of neurogenesis, the creation of new neurons and integration into existing neural networks in the brain. This process is essential to learning and memory. Researchers here investigate the effects of exercise on neurogenesis in mice by labeling neurons in order to determine the contribution of adult neurogenesis to neural networks in the areas of the brain important to memory.

Exercise may prevent or delay aging-related memory loss and neurodegeneration. In rodents, running increases the number of adult-born neurons in the dentate gyrus (DG) of the hippocampus, in association with improved synaptic plasticity and memory function. However, it is unclear if adult-born neurons remain fully integrated into the hippocampal network during aging and whether long-term running affects their connectivity.

To address this issue we labeled proliferating DG neural progenitor cells with retrovirus expressing the avian TVA receptor in 2-month-old sedentary and running male C57Bl/6 mice. More than six months later, we injected EnvA-pseudotyped rabies virus into the DG as a monosynaptic retrograde tracer, to selectively infect TVA expressing 'old' new neurons. We identified and quantified the direct afferent inputs to the adult-born neurons within the hippocampus and (sub)cortical areas.

Here we show that long-term running substantially modifies the network of the neurons generated in young adult mice upon middle-age. Exercise increases input from hippocampal interneurons onto 'old' adult-born neurons, which may play a role in reducing aging-related hippocampal hyperexcitability. In addition, running prevents the loss of adult-born neuron innervation from perirhinal cortex, and increases input from subiculum and entorhinal cortex, brain areas that are essential for contextual and spatial memory. Thus, long-term running maintains the wiring of 'old' new neurons, born during early adulthood, within a network that is important for memory function during aging.

Link: https://doi.org/10.1523/ENEURO.0084-23.2023

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