Antibiotic-mediated gut microbiota depletion affects behavioral and neuronal correlates of spatial cognition

Abstract

Trillions of microbes —comprising communities of bacteria, viruses, fungi, and other microorganisms— inhabit the gastrointestinal tract. Known as gut microbiota, these microorganisms are central to human health. Growing evidence connects imbalances of microbial communities with several neurological and psychiatric conditions, and signals to the modulating role of gut bacteria on brain function, including learning and memory. However, how the microbiota influences cognitive behavior remains unclear. Here, we investigated whether gut microbiota depletion disrupts the behavioral and neuronal correlates of spatial cognition. We depleted gut bacteria in mice by giving a cocktail of non-absorbable antibiotics and characterized 1) learning and memory performance in modalities of a place avoidance task with different cognitive demands and 2) Arc and c-Fos-expressing neuronal ensembles in the supra and infrapyramidal blades of the dentate gyrus. We found impaired learning and memory performance in place avoidance tasks that require high, but not low, cognitive demand and blade-specific alterations in Arc and c-Fos-expressing granule cell ensembles with microbiota depletion. Our results suggest that gut microbial signaling may regulate the expression of neural mechanisms underlying cognitive control.