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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 \u201cold\u201d 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 \u201cold\u201d 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 \u201cold\u201d new neurons, born during early adulthood, within a network that is important for memory function during aging.<\/jats:p>","DOI":"10.1523\/eneuro.0084-23.2023","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T17:50:21Z","timestamp":1684173021000},"page":"ENEURO.0084-23.2023","source":"Crossref","is-referenced-by-count":14,"title":["Running throughout Middle-Age Keeps Old Adult-Born Neurons Wired"],"prefix":"10.1523","volume":"10","author":[{"given":"Carmen","family":"Vivar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5290-9142","authenticated-orcid":false,"given":"Ben","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Pinto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Janke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5727-434X","authenticated-orcid":false,"given":"Henriette","family":"van Praag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"2023052210550712000_10.5.ENEURO.0084-23.2023.1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20810"},{"key":"2023052210550712000_10.5.ENEURO.0084-23.2023.2","unstructured":"Amaral D , Lavenex P (2007) Hippocampal neuroanatomy. 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