REGION-SPECIFIC MATURATION OF PERINEURONAL NETS IN PRIMARY CORTICAL AREAS OF THE DEVELOPING HUMAN BRAIN

Perineuronal nets (PNNs) are condensed extracellular matrix structures that envelop specific neuronal populations contributing to synaptic stabilization, modulation of plasticity, and closure of critical developmental windows. Although the timing and functional significance of PNN maturation have been well characterized in animal models, data on their formation in the developing human cerebral cortex remain scarce. In this study, the spatiotemporal progression of PNN development and condensation was investigated in postmortem perinatal and postnatal human brains, focusing on primary cortical areas. The spatiotemporal expression of PNNs was shown using the general marker Wisteria floribunda agglutinin (WFA). In addition, Lycopersicon esculentum lectin (LEL) and Datura stramonium lectin (DSL) were used to reveal a diverse glycosylation pattern associated with the extracellular matrix in circuit specification. During the perinatal period, WFA labelling was diffusely present in all examined primary cortical regions in the subplate remnant and layer VI, while occasionally exhibiting weak perisomatic staining, i.e., early condensations. During the early postnatal period, WFA labelling showed progressive condensation into defined adult-like PNN structures, primarily localized in layers IV-VI, while diffuse WFA labelling persisted in the deepest cortical layers. On the other hand, DSL and LEL showed more prolonged and widespread diffuse labelling throughout the observed periods. These findings demonstrate that the dynamic of PNN differentiation in human primary cortices is region-specific and molecularly heterogeneous during cortical development. (Funds: Croatian Science Foundation IP-2024-05-4135; DOK-NPOO-2023-10-7312; PK.1.1.10.0009)