Antibiotic-induced gut dysbiosis leads to activation of microglia and impairment of cholinergic gamma oscillations in the hippocampus

Antibiotics are widely applied for the treatment of bacterial infections, but their long-term use may lead to gut flora dysbiosis and detrimental effects on brain physiology, behavior as well as cognitive performance. Still, a striking lack of knowledge exists concerning electrophysiological correlates of antibiotic-induced changes in gut microbiota and behavior. Here, we investigated changes in the synaptic transmission and plasticity together with behaviorally-relevant network activities from the hippocampus of antibiotic-treated mice. Prolonged antibiotic treatment led to a reduction of myeloid cell pools in bone marrow, circulation and those surveilling the brain. Circulating Ly6C(hi) inflammatory monocytes adopted a proinflammatory phenotype with increased expression of CD40 and MHC II. In the central nervous system, microglia displayed a subtle activated phenotype with elevated CD40 and MHC II expression, increased IL-6 and TNF production as well as with an increased number of Iba1 + cells in the hippocampal CA3 and CA1 subregions. Concomitantly, we detected a substantial reduction in the synaptic transmission in the hippocampal CA1 after antibiotic treatment. In line, carbachol-induced cholinergic gamma oscillation were reduced upon antibiotic treatment while the incidence of hippocampal sharp waves was elevated. These alterations were associated with the global changes in the expression of neurotrophin nerve growth factor and inducible nitric oxide synthase, both of which have been shown to influence cholinergic system in the hippocampus. Overall, our study demonstrates that antibiotic-induced dysbiosis of the gut microbiome and subsequent alteration of the immune cell function are associated with reduced synaptic transmission and gamma oscillations in the hippocampus, a brain region that is critically involved in mediation of innate and cognitive behavior.