Structural maturation of cortical perineuronal nets and their perforating synapses revealed by superresolution imaging

Significance Particular inhibitory neurons containing parvalbumin (PV) play a critical role in determining the time course by which experience shapes developing brain circuits. Embedded deep within cortical gray matter, extracellular matrices enwrapping PV-positive (PV+) cells have remained difficult to study partly due to the small length scale on which they are organized. To overcome such challenges, we used a superresolution fluorescence imaging approach to visualize these perineuronal nets (PNNs), a specialized form of the extracellular matrix critical for maintaining mature PV+ neuron function and their synaptic inputs. We quantified changes that define PNN structure and identified specific synaptic defects in a mouse model lackingMeCP2 , the causative gene for Rett syndrome, a regressive neurodevelopmental disorder.