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.Amy C. Reichelt, Dominic J. Hare, Timothy J. Bussey, and Lisa M. Saksid