PT - JOURNAL ARTICLE AU - Billy Y.B. Lau AU - Dana E. Layo AU - Brett Emery AU - Matthew Everett AU - Anushree Kumar AU - Parker Stevenson AU - Kristopher G. Reynolds AU - Andrew Cherosky AU - Sarah-Anne H. Bowyer AU - Sarah Roth AU - Delaney G. Fisher AU - Rachel P. McCord AU - Keerthi Krishnan TI - Lateralized expression of cortical perineuronal nets during maternal experience is dependent on MECP2 AID - 10.1523/ENEURO.0500-19.2020 DP - 2020 Apr 22 TA - eneuro PG - ENEURO.0500-19.2020 4099 - http://www.eneuro.org/content/early/2020/04/21/ENEURO.0500-19.2020.short 4100 - http://www.eneuro.org/content/early/2020/04/21/ENEURO.0500-19.2020.full AB - 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 (PNNs), the adult mouse brain exhibits restricted plasticity and maturity. Mature PNNs are typically considered to be stable structures that restrict synaptic plasticity on cortical parvalbumin+ GABAergic neurons. Changes in environment (i.e. novel behavioral training) or social contexts (i.e. motherhood) are known to elicit synaptic plasticity in relevant neural circuitry. However, little is known about concomitant changes in the PNNs surrounding the cortical parvalbumin+ GABAergic neurons. Here, we show novel changes in PNN density in the primary somatosensory cortex (SS1) of adult female mice after maternal experience (called Surrogate, Sur), using systematic microscopy analysis of a whole brain region. On average, PNNs were increased in the right barrel field and decreased in the left forelimb regions. Individual mice had left hemisphere dominance in PNN density. Using adult female mice deficient in methyl-CpG-binding protein 2 (MECP2), an epigenetic regulator involved in regulating experience-dependent plasticity, we found that MECP2 is critical for this precise and dynamic expression of PNN. Adult naïve Mecp2-heterozygous females (Het) had increased PNN density in specific subregions in both hemispheres before maternal experience, compared to wildtype (WT) littermate controls. The laterality in PNN expression seen in naïve Het was lost after maternal experience in Surrogate Het mice, suggesting possible intact mechanisms for plasticity. Together, our results identify subregion and hemisphere-specific alterations in PNN expression in adult females, suggesting extracellular matrix plasticity as a possible neurobiological mechanism for adult behaviors in rodents.Significance Statement Perineuronal nets (PNNs) are extracellular matrix structures that surround cortical parvalbumin+ fast spiking GABAergic interneurons and synapses. They have long been considered stable structures that restrict synaptic plasticity. Removal of PNNs by enzymes reactivates plasticity in the rodent visual and auditory cortices and in the amygdala. However, it is currently unknown if PNNs in adult brains undergo changes in expression under normal physiological conditions, similar to synaptic plasticity mechanisms. If they do, PNNs may not be very stable structures as they are perceived. We provide evidence that mature PNNs in the adult mouse primary somatosensory cortex show dynamic expression changes in a hemisphere-specific, subregion-specific manner after maternal experience and are regulated by methyl-CpG-binding protein 2 (MECP2).