The gut microbiota has emerged as a novel regulator of system-wide physiology. Intriguingly, the microbiome play an important role in brain related processes: myelination, microglia maturation, neurogenesis, blood-brain-barrier permeability, influencing behavioral outcomes. Despite this evidence, little is known about how intestinal bacteria impinge on neuronal function and especially, nobody has ever explored if there is a link between sensory system development/plasticity and gut microbiota. The new key concept emerging from my project is that changes in the microbiota composition could modulate neural circuit function in sensory systems resulting in altered brain plasticity.
To address this issue, GaMePLAY focused on the visual system. Manipulation of visual inputs results in distinctive behavioral consequences in young and adult subjects. The effect of sensory inputs’ deprivation, obtained via monocular deprivation (MD, the suture of an eye), is highly evident only during the critical period for ocular dominance (OD) plasticity, a postnatal time-window in which neuronal circuits are particularly sensitive to experience. 3 days of MD in juvenile mice are sufficient to cause a plastic phenomenon called OD shift. Visual cortical plasticity and, in general, brain plasticity displays a significant decrease in adulthood.
The paradigm exploited to investigate how changes in gut microbiota composition could affect brain plasticity was the so-called enriched environment (EE). EE consists in a specific animal housing condition characterized by elevated social interactions, cognitive, sensory and motor stimulations. EE has been demonstrated to affect brain plasticity and behaviour, acting during youth, adulthood and aging, and to enhance OD plasticity. Finally, EE has positive effects on a variety of neurological disorder preclinical models (e.g. Alzheimer, Parkinson disease, stroke).
It is becoming clear that the gut microbiota influence brain function and finally behaviour. The data collected by GaMePLAY are helping to understand the microbiota role on brain plasticity. My results show how the faecal transplant of a “pro-plasticity microbiota” enhances brain plasticity in adult rodents, which generally do not display this property. Moreover, the identification of specific bacteria strains might help to discover new probiotics. This is particularly relevant for therapy, with a consequent tremendous impact on society. Indeed, probiotic treatments can be easily applied in humans, opening exciting opportunities for treating neuropsychiatric diseases with microbiota based-therapies.
Objectives:
1)To characterize the gut microbiota at different ages in mice housed in standard (ST) condition or in an EE and to analyse the differences between the two rearing conditions;
2)To investigate the contribution of the gut microbiota to the effects of EE on brain plasticity, studying the visual system;
3)To dissect the mechanisms through which the intestinal microflora affects cortical plasticity.
