Controlling Plasticity in the Human Brain: Role of Perineuronal Nets in Regulating Network Dynamics and the Potential for Plasticity-Based Therapies

Our brains constantly change in response to new sensory stimulation, active learning, or memory formation. This ability to change is known as ‘plasticity’. But the plastic changes are not unlimited. In fact, the level of plasticity in the brain is actively regulated, and in the adult brain, largely inhibited.

Many neurological disorders are related to disruption in the regulation of plasticity: some types of epilepsy are caused by excess levels of plasticity. On the other hand, increased levels of plasticity can improve the function of neural prosthetics or increase recovery after stroke. If we can control the level of neural plasticity, we could develop new ways of treating these disorders.

Before we can control plasticity artificially, we must first understand how our brains regulate plasticity naturally. One example is how the brain limits plasticity is perineuronal nets (PNNs). PNNs are protein-sugar complexes that surround some neurons. The timing is specific —PNNs form at the end of periods of high plasticity or “critical periods” during early stages of development. The removal of PNNs restores high levels of plasticity. Still, the mechanism by which PNNs limit plasticity is not known.

Here we present some of the first work on how PNNs regulate plasticity functionally. Specifically, we show that removing PNNs makes the brain more excitable (i.e. it responds more to the same input). This provides us with a glimpse of ways that we may, in the future, be able increase regenerative and plastic capacities of the human brain.