Both functional and structural plasticity of synaptic connections persists throughout the lifetime, although appearing to diminish

over time. The century-old idea that learning and memory involve structural remodeling of synaptic connections has gained increasing experimental support (Caroni et al., 2012). Long-term in vivo measurements of identified spines in the adult rodent cortices showed a small fraction of synapses undergo turnover (Grutzendler et al., selleck chemical 2002 and Trachtenberg et al., 2002). However, behavioral learning (Xu et al., 2005 and Yang and Zhou, 2009) and visual experience (Hofer et al., 2009) lead to formation of new spines that remain stable for many months, potentially serving as long-lasting memory traces. In essence, activity-dependent sculpting of developing circuits represents learning/memory of early experiences, whereas the residual developmental plasticity provides the learning/memory capacity of the mature brain. Maturation of inhibitory circuits is essential for opening learn more the critical period

in V1 during postnatal development (Hensch, 2004), when monocular deprivation could induce expansion and retraction of thalamocortical axon arbors for inputs carrying information from the open and closed eyes, respectively. The critical period becomes permanently closed after a few weeks (in rodents) through a mechanism that remains to be fully characterized (Espinosa Olopatadine and Stryker, 2012). Interestingly, recent findings showed that critical-period plasticity could be reactivated in the adult nervous system. Resetting excitatory-inhibitory balance (Harauzov et al., 2010 and Maya Vetencourt et al., 2008), removal of growth-inhibitory factors with enzymatic

digestion of extracelluar chondroitin sulfate proteoglygan (CSPGs) (Pizzorusso et al., 2002 and Vorobyov et al., 2013), or genetic deletion of Nogo-66 receptor for myelin membrane associated growth-inhibiting proteins (McGee et al., 2005) or choroids-expressed Otx2 homeoprotein (Spatazza et al., 2013) have all been shown to restore critical-period plasticity in V1 in response to monocular deprivation in mice. These findings suggest that closure of critical period in early development is intimately associated with the formation of the perineuronal net surrounding the neurons and expression of inhibitory myelin factors and other secreted factors, e.g., Otx2 (Spatazza et al., 2013), which stabilize the local circuit. On the other hand, reduced plasticity in the adult brain is not without benefit: it helps the stabilization of synaptic structures and stored memory, as shown by the finding that enzymatic removal of CSPGs in adult rats results in the susceptibility of the fear memory to erasure by extinction (Gogolla et al., 2009).