CDKL5 deficiency results in atypical subregion-specific expression of perineuronal nets in the mouse primary visual cortex

Perineuronal nets (PNNs) in the primary visual cortex (V1) are specialized extracellular matrix structures that form predominantly on parvalbumin+ GABAergic neurons, marking the closure of visual critical period plasticity. More recently, PNNs are used to characterize deficits in critical period plasticity in mouse models for neurodevelopmental disorders such as Rett syndrome, Fragile X syndrome, and CDKL5 deficiency disorder. Within the mouse V1, studies typically focus on the expression and function of PNNs within the binocular zone, though PNNs are expressed in other subregions of the V1. The expression and role of these PNNs in other subregions are unknown. Here, we performed a systematic whole V1 characterization of PNN expression using Wisteria floribunda agglutinin (WFA) staining, with hemisphere-, subregion-, and anatomical axes-specificity, using a null male mouse model for CDKL5 deficiency disorder during the visual critical period. Patients with CDKL5 deficiency disorder often exhibit cerebral cortical visual impairment, though the underlying mechanisms are unclear. Compared to wild-type controls, Cdkl5-null males show increased WFA expression at both P15 and P30, with nuanced differences in the subregions, suggesting precocious increase in PNN expression in the Cdkl5-null V1. In both genotypes, the binocular zone has significantly higher density of PNNs at both ages, compared to the monocular zone and the rostral V1. These results lay the groundwork to probe the roles for PNNs beyond the binocular zone and cumulatively suggest that, during visual critical period, subregion-specific variations in PNN expression may lead to functional consequences within the Cdkl5-null cortex.