Perineuronal nets (PNNs) decrease neuroplasticity, increase stability of neural systems, and are key to ending the neurodevelopmental critical period. PNNs are found throughout the brain, including the mediodorsal (MD) thalamus, a key region in cortico-thalamo-cortical communication with the prefrontal cortex (PFC). I examined the structure and location of PNN elements relative to axons in the MD thalamus from post-mortem human brain tissue in three normal individuals. Using electron microscopy and two-dimensional analysis, my results showed that about a third of axons have a consistent distribution of the PNN element brevican. A vital component of PNNs, the chondroitin sulfate proteoglycan (CSPG) brevican was found within the cytoplasm, within the myelin, and outside the myelin along the length of axons. Three-dimensional analyses and axon reconstructions showed that the quantity of brevican varied periodically along axons in a wave-like manner. These findings suggest a model for the arrangement of brevican in a weaving pattern through myelin, cytoplasm, and external surface of axons. This model of PNN elements has various functional implications, including influence on the growth and function of axons, ion homeostasis along the axon, and the ability of neurons to produce and transmit action potentials. These structures likely have a significant impact on the function of MD. The combined influence of PNNs and connections of the MD thalamus with the PFC may play powerful roles in various cognitive disorders, including schizophrenia.

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