TY - JOUR T1 - Running throughout Middle-Age Keeps Old Adult-Born Neurons Wired JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0084-23.2023 VL - 10 IS - 5 SP - ENEURO.0084-23.2023 AU - Carmen Vivar AU - Ben Peterson AU - Alejandro Pinto AU - Emma Janke AU - Henriette van Praag Y1 - 2023/05/01 UR - http://www.eneuro.org/content/10/5/ENEURO.0084-23.2023.abstract N2 - 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 whether 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 two-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 these 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. ER -