Aging is known to be associated with hippocampus-dependent memory decline, but the underlying causes of this age-related memory impairment are not yet elucidated. Here we show that the colonization of mice with the gut microbiota from aged, but not young animals is sufficient to trigger profound hippocampal alterations including astrogliosis, decreased adult neurogenesis, decreased novelty-induced neuronal activation and impairment in hippocampal-dependent memory. Similar alterations were reported in mice following the transfer of microbiota from aged human healthy donors. To decipher the mechanisms involved in mediating these microbiota-induced effects on brain functioning, we mapped the neuronal activity patterns and report that aged-microbiota transplantation reduced neuronal activity upstream to the vagus nerve. Targeted pharmacogenetic manipulation of the ascending branch of the vagus nerve demonstrated that the mere decrease in vagal activity was also detrimental to hippocampal functions. In contrast, increasing vagal activity alleviated the adverse effects of age-associated microbiota transfer on hippocampal functions and reinstated normal hippocampal memory in aged mice. We conclude that vagus nerve stimulation is a potential therapeutic strategy to lessen microbiota-dependent age-associated impairments in hippocampal functions.
bioRxiv Subject Collection: Neuroscience