Perineuronal net
Perineuronal nets (PNNs) are specialized extracellular matrix structures responsible for synaptic stabilization in the adult brain.
Studies of the rat brain have shown that the cortex contains high numbers of PNNs in the motor and primary sensory areas and relatively fewer in the association and limbic cortices.
[2] In the cortex, PNNs are associated mostly with inhibitory interneurons and are thought to be responsible for maintaining the excitatory/inhibitory balance in the adult brain.
However, Ramón y Cajal credits Golgi with the discovery of PNNs because he was the first to draw attention to them and gave the first precise description in 1893.
Despite debating the topic, Ramón y Cajal claimed that the perineuronal net was simply a staining artifact derived from the coagulation of extracellular fluids.
Interest arose in the 1960s when several authors drew attention to the presence of periodic-acid-Schiff-positive (PAS-positive) material surrounding nerve cells.
However, the authors clung to the idea that the material was intricately connected to the blood–brain barrier and failed to see the similarities it had with the perineuronal net described by Golgi.
Interest only rose again in the past few decades when it was discovered that PNNs constitute markers for physiologically mature neurons.
[4] PNNs are composed of a condensed matrix of chondroitin sulfate proteoglycans, molecules that consist of a core protein and a glycosaminoglycan (GAG) chain.
The CS-GAG chains associated with PNNs differs from those found floating in the extra-cellular matrix in a noncondensed form.
PNNs are composed of brevican, neurocan, versican, aggrecan, phosphacan, hyaluronan, tenascin-R and various link proteins.
A fine regulation of axonal and dendritic growth is required in the adult CNS to preserve important connections while still allowing for structural plasticity.
In order to assess the physiological role of PNNs in the undamaged CNS, ChABC was injected in the healthy cerebellum of adult rats.
Within 42 days, the expression of CSPGs gradually recovered, at which point axon outgrowth regressed, indicating that there was no significant formation of stable synaptic contacts.
[9] Cell surface proteins, including neurotransmitter receptors, are highly mobile in the plasma membrane due to lateral diffusion.
Diffusion of the desensitized receptor for the exchange of a naive functional one increases synaptic fidelity during fast repetitive stimulation.
PNNs compartmentalize the neuronal surface and act as lateral diffusion barriers for AMPARs, limiting synaptic exchange.
[3] PNNs, with their strongly negative charge, may serve as cation exchangers preventing the free diffusion of potassium or sodium ions.
Due to the spatial, temporal, and numerical disproportions between Na+ influx and K+ efflux, the PNN provides a possible buffering system for extracellular cations.
[13] In the rat brain and spinal cord, the expression of various CSPGs (brevican, versican, neurocan, and NG2) increases after injury.
In contrast, in early postnatal development, extinction of a conditioned fear response leads to memory erasure.
In the adult animal, degradation of PNNs in the amygdala with ChABC renders subsequently acquired fear memories susceptible to erasure.
[18] Following seizures, there is a decrease in phosphacan and phosphacan-positive PNNs and an increase in cleaved brevican in the temporal lobe and hippocampus.
