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

Cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder is an X-linked neurodevelopmental disorder, where children exhibit motor, speech, cognitive and visual deficits during development as well as early onset of seizures and infantile spasms. CDKL5 disorder results from de novo mutations in CDKL5, which phosphorylates proteins including MECP2, an epigenetic regulator of critical period plasticity. How mutations in CDKL5 gene result in these neurological deficits is unknown. Using a male CDKL5-null mouse model, we systematically characterize the expression of perineuronal nets, which are extracellular matrix structures surrounding parvalbumin+ GABAergic neurons in the primary visual cortex. Perineuronal nets (PNNs) are considered to be barriers to synaptic plasticity, particularly at the end of critical period plasticity in binocular zone. In CDKL5-null male visual cortex, here we report an increase in high-intensity PNN expression in the binocular zone, a decrease in overall PNN expression in the monocular zone, and no differences in PNN expression in rostral V1. These results suggest that at the closure of the visual critical period plasticity, subregion-specific variations in PNN expression lead to functional differences in synaptic plasticity and ultimately, changes in visual function in male CDKL5- null mice. Additionally, the systematic characterization of subregion-specific expression patterns of perineuronal nets lay the groundwork for further studies to probe the roles for perineuronal nets beyond the binocular zone of the mouse primary visual cortex. ### Competing Interest Statement The authors have declared no competing interest.