Perineuronal nets (PNNs) are a particular mesh-like aggregation of extracellular matrix molecules which form around neuronal soma and proximal projections during postnatal development. Fast-spiking parvalbumin-positive GABAergic interneurons (PVIs) are the type of neurons preferentially enveloped in many cortical areas, and their coverage is considered a sign of maturity. The last decades have seen a gradual and increasing recognition of the remarkable role of PNN in controlling plasticity, and alterations of PNN expression and PVI density have been described in patients and animal models for various neuropsychiatric and neurodevelopmental disorders. Despite that, little is known yet about differences in PNN amount, morphology, distribution and association with specific cell types in the whole brain. In the Fragile X syndrome (FXS), the loss of FMRP activity provokes an upregulation of Matrix Metallopeptidases 9 (MMP-9) translation that leads to increased PNN digestion. However, other mechanisms may be involved in the reduction of PNNs and in the maturation of PVIs in different brain areas. FXS-dependent PNN and PVI alterations may affect the activity and plasticity of brain areas controlling different physiological and behavioral functions. Here we have developed a customized method for brain-wide 3D reconstruction of histologically stained serial sections followed by high-throughput imaging analysis, to better characterize PNN and parvalbumin expression in the brain of Fmr1KO and control mice.

More information:

• https://www.nico.ottolenghi.unito.it/eng/Research/Research-Groups/Neuropsychopharmacology/Researchers/Ilaria-Bertocchi