Microbial memories: Sex-dependent impact of the gut microbiome on hippocampal plasticity.

Germ-free rodents, raised in the absence of a measurable gut microbiome, have been a key model to study the microbiome-gut-brain axis. Germ-free mice exhibit marked behavioural and neurochemical differences to their conventionally raised counterparts. It is as yet unclear how these neurochemical differences lead to the behavioural differences. Here, we test the electrophysiological properties of hippocampal plasticity in adult germ-free mice and compare them to conventionally raised counterparts. Whilst basal synaptic efficacy and pre-synaptic short-term plasticity appear normal, we find a striking alteration of hippocampal long-term potentiation specifically in male germ-free slices. However, the spike output of these neurons remains normal along with altered input-output coupling, potentially indicating homeostatic compensatory mechanisms, or an altered excitation/inhibition balance. To our knowledge this is the first time the electrophysiological properties of the hippocampus have been assessed in a microbiome deficient animal. Our data indicate that the absence of a microbiome alters integration of dendritic signalling in the CA1 region in mice.