, 1998; Carulli et al., 2007; Zimmermann & Dours-Zimmermann, 2008). The ECM of the embryonic and juvenile brain is permissive and supportive for neurogenesis and gliogenesis, cell migration, axonal outgrowth and axonal pathfinding, as well as for synaptogenesis and synaptic rearrangements (Bandtlow & Zimmermann, 2000; Faissner et al., 2010). In contrast, the adult ECM is nonpermissive

for axonal outgrowth and inhibits regeneration and major reorganization processes in the adult CNS (Galtrey & Fawcett, 2007; Fawcett, 2009). In addition to a variety of other factors, CSPGs of the lectican family including brevican display an inhibitory activity on neurite outgrowth (Zurn & Bandtlow, 2006; Quaglia et al., 2008), and the removal of ECM by chondriotinase ABC constitutes a way to promote functional buy MK-1775 recovery in the injured brain (Crespo et al., 2007; Galtrey & Fawcett, 2007). The implementation of the

adult ECM coincides with the end of the critical period (Lander et al., 1997; Fawcett, 2009), the time window during which neuronal circuits are shaped and refined by experience. The critical periods of enhanced structural and functional synaptic plasticity differ from brain area to brain area and from species to species, and can last for months to years in primates including humans (Hensch, 2004). The restriction PD-1/PD-L1 signaling pathway in regenerative and reorganizational plasticity of the CNS, which has evolved in higher vertebrates only, must provide an evolutionary advantage over lower vertebrates, which have largely retained this plasticity. This evolutionary benefit may include the suppression of regenerative processes that are time- and energy-consumptive and though beneficial for the individual not helpful for the survival of the population, and/or the preservation of costly acquired hardwired connections that are essential for the rapid

experience-based processing of information in complex nervous systems. Nonetheless the adult nervous system retains a eltoprazine remarkable synaptic plasticity that is partly based on the local restoration of a ‘juvenile’ environment. Here, we will briefly survey the present knowledge about structure and functions of the adult ECM and then discuss potential mechanisms by which the adult ECM restricts juvenile synaptic plasticity and how this plasticity may be locally restored by the release or activation of ECM-removing or -modifying enzymes. The brain’s ECM has a complex history. Although perineuronal nets (PNNs) were discovered, as prominent structures surrounding neurons, by the pioneers of brain cell biology including Camillo Golgi and Santiago Ramon y Cajal (for review see Celio et al.