GERM-FREE MICE SHOW ALTERATIONS OF SYNAPTIC TRANSMISSION AND PLASTICITY

The bidirectional communication between the gut microbiome and the brain has attracted growing attention. Alterations in microbial composition have been implicated in both physiological brain function and the pathophysiology of neuropsychiatric and neurodegenerative disorders. Despite substantial progress in the field, the mechanisms by which the microbiome modulates synaptic transmission and neuronal plasticity remain poorly understood. To investigate the causal impact of the microbiome on brain physiology, we employed germ-free (GF) mice devoid of all living microorganisms and compared them to specific-pathogen-free (SPF) control mice. We performed ex vivo whole-cell patch-clamp recordings from superficial layer (L2/3) pyramidal neurons in the medial prefrontal cortex (mPFC) of adult mice to assess functional aspects of excitatory neurotransmission. In addition, chemically induced long-term potentiation (cLTP) was used to evaluate the capacity of these neurons to undergo synaptic plasticity. Whole-cell recordings revealed that baseline excitatory synaptic transmission in GF mice was comparable to that observed in SPF controls. Consistently, post hoc morphological analyses showed no significant differences in dendritic architecture between groups. In contrast, neurons from microbiome-deficient mice exhibited a pronounced impairment in their ability to express synaptic plasticity following cLTP induction. Together, these findings indicate that while the absence of a microbiome does not affect baseline excitatory neurotransmission or dendritic structure in mPFC pyramidal neurons, it significantly compromises synaptic adaptability. Our results highlight a critical role of the gut microbiome in regulating synaptic plasticity and underscore its importance for physiological brain function.