The gut-brain vagal axis scales hippocampal memory processes and plasticity

The vagus nerve serves as an interoceptive relay between the body and the brain. Despite its well-established role in feeding behaviors, energy metabolism, and cognitive functions, the intricate functional processes linking the vagus nerve to the hippocampus and its contribution to learning and memory dynamics remain still elusive. Here, we investigated whether and how the gut-brain vagal axis contributes to hippocampal learning and memory processes at behavioral, functional, cellular, and molecular levels. Our results indicate that the integrity of the vagal axis is essential for long-term recognition memories, while sparing other forms of memory. In addition, by combing multi-scale approaches, our findings show that the gut-brain vagal tone exerts a permissive role in scaling intracellular signaling events, gene expressions, hippocampal dendritic spines density as well as functional long-term plasticities (LTD and LTP). These results highlight the critical role of the gut-brain vagal axis in maintaining the spontaneous and homeostatic functions of hippocampal ensembles and in regulating their learning and memory functions. In conclusion, our study provides comprehensive insights into the multifaceted involvement of the gut-brain vagal axis in shaping time-dependent hippocampal learning and memory dynamics. Understanding the mechanisms underlying this interoceptive body-brain neuronal communication may pave the way for novel therapeutic approaches in conditions associated with cognitive decline, including neurodegenerative disorders. HighlightsO_LIThe gut-brain vagal axis contributes to long-term recognition memories C_LIO_LIThe gut-brain vagal axis is dispensable for short-term memories C_LIO_LIThe vagal axis regulates molecular and signaling dynamics in the hippocampus C_LIO_LIThe gut-brain vagal tone shapes the structural density of hippocampal dendritic spines C_LIO_LIThe gut-brain vagal tone ensures physiological forms of synaptic plasticity C_LI