Converting juvenile into adult plasticity: a role for the brain's extracellular matrix.

In higher vertebrates, the extracellular matrix (ECM) wrapping cells of the adult brain differs significantly from that of the developing and juvenile brain. The mature ECM is established at the end of critical periods for wiring and it restricts the regenerative potential and constrains the plasticity of the adult brain. In particular, perineuronal nets, elaborate ECM structures that surround distinct neurons and wrap synapses, are hallmarks of the adult brain and seem to massively affect brain plasticity. Why have these, at first glance futile, limitations evolved? What is the return for these drawbacks? What are the mechanisms of restriction and how is adult plasticity implemented? Recent progress both at the systemic level and at the molecular physiological level has shed some new light on these questions. In this review we will survey the evidence for potential functions of the adult ECM in making established brain features, including imprinted memories, resistant to extinction, and we will discuss potential mechanisms by which the ECM limits juvenile and implements adult plasticity. In particular we will focus on some aspects of adult ECM function. First we will discuss its influence on diffusion of cations in the extracellular space and on volume transmission, second we will consider its potential role in regulating the lateral diffusion of cell surface receptors and finally we will discuss mechanisms to locally modulate ECM functions.