Perineuronal Nets: Plasticity, Protection, and Therapeutic Potential

The relationship between neurons and perineuronal nets (PNNs) is attracting attention as a central mechanism controlling brain plasticity. In the cortex, PNNs primarily surround inhibitory parvalbumin interneurons, playing roles as both a regulator of synaptic plasticity and a protective barrier. PNNs have a delayed developmental trajectory and are key components in the closure of critical periods of heightened neuroplasticity. In animal models, manipulating PNNs outside this critical window can enhance cognition, suggesting a potentially therapeutic approach for attenuating cognitive decline. However, the crucial role of PNNs in plasticity and protection means that such therapeutic modulation must strike a careful balance: manipulation of PNNs to promote plasticity may have unintended negative consequences resulting from excessive plasticity or from exposure of neurons to neurotoxins.