Reelin seems to exert important functions during the transition from the developing to the mature brain. Thus it has been implicated in the control of the subunit composition of somatic NMDA receptors during hippocampal maturation (Sinagra et al., 2005). Moreover, the same group reported recently

that reelin secreted by GABAergic interneurons is responsible for maintaining the adult NMDA receptor composition and that blocking reelin secretion reversibly increases small molecule library screening the fraction of juvenile NR2B-containing NMDA receptors. This effect can be rescued by supplementing exogenous reelin (Campo et al., 2009). Finally, reelin controls the surface trafficking of NR2B-containing NMDA receptors. As shown by single-particle tracking, inhibition of reelin function reduced the surface mobility of these receptors and increased their synaptic dwell time signaling pathway (Groc et al., 2007). This effect depended on beta1-containing integrin receptors, which are supposed to co-operate with APOE2Rs and/or VLDLRs. Currently it is unclear whether the protease activity of reelin plays a role in these processes.

The ECM of the adult brain has features that differ considerably from those of the developing and the juvenile brain. Its implementation has dramatic consequences for the brain physiology. This becomes most obvious in the severe reduction of the regenerative potential that has long been recognized. FER Another feature to which the adult ECM contributes is the closure of the critical period, which may serve the stabilization of brain wiring after a period of experience-driven refinement. This

has been impressively documented by the experiments of Pizzorusso et al. (2002) for the visual cortex. Recent experiments on the extinction of fear memories (Gogolla et al., 2009) suggest there is much more to be disclosed. These experiments suggest that memory acquisition differs between juvenile and adult brains and that adult structures of the hyaluronan–CSPG-based ECM are essential for an imprinted memory to bad experience. One does not have to be an augur to predict that we will face a multitude of studies that will unravel the function of PNNs and perisynaptic ECM structures in long-term memory processes. As we have tried to illustrate in our article, the first details are emerging about how molecular and cellular mechanisms govern the adult ECM implementation of its functionality. A major principle seems to be to restrict lateral diffusion of cell surface molecules and to change the diffusion conditions, i.e. the tortuosity, for ions, small molecules and even macromolecules in the extracellular space. This in turn affects a large variety of parameters including calcium homeostasis, volume transmission of glutamate and other charged messengers, and local concentrations of signaling molecules.