Dynamic perineuronal net expression during learned maternal behavior is cortical hemisphere-specific and dependent on methyl-CpG-binding protein 2

Cortical neuronal circuits along the sensorimotor pathways are shaped by experience during critical periods of heightened plasticity in early postnatal development. After closure of critical periods, measured histologically by the formation and maintenance of extracellular matrix structures called perineuronal nets (PNN), the adult mouse brain exhibits restricted plasticity and maturity. Mature PNN are typically considered to be stable structures that restrict synaptic plasticity on cortical parvalbumin+ GABAergic neurons. However, changes in environment, such as novel behavioral training or social contexts such as motherhood, elicit synaptic plasticity in relevant neural circuitry. Currently, it is unclear if extracellular matrix plasticity, as measured by PNN density, occurs in such social contexts in adult wildtype female mice. Here, we found novel PNN density changes in the primary somatosensory cortex (SS1) in a hemisphere-, subregion-specific manner after a maternal behavior task, using systematic whole brain region microscopy analysis. Furthermore, we found hemispheric bias in PNN density in individual mice. Using adult female mice deficient in methyl-CpG-binding protein 2 (MECP2), an epigenetic regulator, we found that MECP2 is critical for this precise and dynamic expression of PNN.