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Here, we show that fecal microbiota transplantation (FMT) from aged, but not young, animal donors into young mice is sufficient to trigger profound hippocampal alterations, including astrogliosis, decreased adult neurogenesis, decreased novelty-induced neuronal activation, and impairment in hippocampus-dependent memory. Furthermore, similar alterations were reported when mice were subjected to an FMT from aged human donors. To decipher the mechanisms involved in mediating these microbiota-induced effects on brain function, we mapped the vagus nerve\u2013related (VN-related) neuronal activity patterns and report that aged FMT animals showed a reduction in neuronal activity in the ascending-VN output brain structure, whether under basal condition or after VN stimulation. Targeted pharmacogenetic manipulation of VN-ascending neurons demonstrated that the decrease in vagal activity is detrimental to hippocampal functions. In contrast, increasing vagal ascending activity alleviated the adverse effects of aged mouse FMT on hippocampal functions and had a promnesic effect in aged mice. Thus, pharmacogenetic VN stimulation is a potential therapeutic strategy to lessen microbiota-dependent age-associated impairments in hippocampal functions.<\/jats:p>","DOI":"10.1172\/jci.insight.147700","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T12:00:42Z","timestamp":1655985642000},"source":"Crossref","is-referenced-by-count":47,"title":["Age-associated gut microbiota impairs hippocampus-dependent memory in a vagus-dependent manner"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2049-256X","authenticated-orcid":true,"given":"Damien","family":"Rei","sequence":"first","affiliation":[{"name":"Institut Pasteur de Paris, Paris Cit\u00e9 University, CNRS UMR 3571, Perception and Memory Unit, Paris, 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