Robust Hippocampal Synaptic Plasticity Despite Gut Microbiota Depletion in Adult Mice

The microbiota-gut-brain axis describes the bidirectional communication between the brain and the trillions of microorganisms living in the gut. Moreover, current evidence suggests that this axis can influence host behaviour and brain physiology. Previously we have shown that adult mice that have not been exposed to microbes throughout their lives display sex-specific deficits in hippocampal synaptic plasticity. However, it is not known whether this phenomenon originates during neurodevelopment or whether similar effects could be recreated with microbiome depletion in adulthood. Therefore, we explored the vulnerability of hippocampal synaptic function to altered microbiome signals, depleting the microbiome of male and female mice for 2 weeks with either an antibiotic cocktail or a single antibiotic added to drinking water. The antibiotic cocktail contained a variety of antibiotics including broad-spectrum antibiotics to ensure widescale microbiota depletion (ampicillin, vancomycin and imipenem). In addition, a more targeted depletion of Gram-positive gut bacteria was conducted using the gut-restricted antibiotic vancomycin. Ex vivo hippocampal electrophysiology measures of basal synaptic efficacy, short-term plasticity, and long-term potentiation (LTP) were then examined. We found that there was no effect of antibiotic administration on any of these measures, demonstrating the robustness of these hippocampal circuits to microbiome depletion during early adulthood. Taken together, this shows the ability of adult hippocampal plasticity to withstand a gut microbiome insult.