The gut microbiota of environmentally enriched mice regulates visual cortical plasticity

Exposing animals to an enriched environment (EE) has dramatic effects on brain structure, function, and plasticity. The poorly known EE-derived signalsmediating the EE effects are thought to be generated within the central nervous system. Here, we shift the focus to the body periphery, revealing that gut microbiota signals are crucial for EE-driven plasticity. Developmental analysis reveals striking differences in intestinal bacteria composition between EE and standard rearing (ST) mice, as well as enhanced levels of short-chain fatty acids (SCFA) in EE mice. Depleting the microbiota of EE mice with antibiotics strongly decreases SCFA and prevents activation of adult ocular dominance plasticity, spine dynamics, and microglia rearrangement. SCFA treatment in ST mice mimics EE induction of ocular dominance plasticity and microglial remodeling. Remarkably, transferring the microbiota of EE mice to ST recipients activates adult ocular dominance plasticity. Thus, experience-dependent changes in gut microbiota regulate brain plasticity.

Automated summary

Exposing animals to an enriched environment (EE) has significant effects on brain structure, function, and plasticity, which are believed to be mediated by signals from the gut microbiota. This study reveals differences in gut bacterial composition and higher levels of short-chain fatty acids (SCFA) in EE mice compared to standard rearing (ST) mice. Depletion of gut microbiota in EE mice reduces SCFA levels and prevents activation of brain plasticity. Treatment with SCFA in ST mice mimics the effects of EE on brain plasticity. Importantly, transferring the gut microbiota from EE mice to ST mice activates brain plasticity. Therefore, changes in gut microbiota due to environmental enrichment play a crucial role in regulating brain plasticity.