the PSD from their original clustering in synaptic puncta, thus increasing their efficacy for cell adhesion. N-cadherin adhesion further stabilizes the synapse by enabling AMPAR-activation-induced spine head expansion. This morphological change helps to prevent further synaptic modifications that could jeopardize the information held by the already existing synaptic connections. Spine head expansion accomplishes this by reducing the NMDAR to AMPAR ratio, creating a proportionally smaller calcium influx, as well as by allowing for faster calcium diffusion out of the spine. The rapid removal of calcium prevents it from initiating the post-translational modifications that would further alter synaptic strength. Overexpression of an N-cadherin mutant incapable of adhesion prevents spine head expansion, demonstrating N-cadherin’s essential role in this process. Regulation of cadherin surface levels, turnover, and stability Regulation mechanisms differ in their synthesis requirements and their temporal initiation. One mode of cadherin regulation is surface stabilization, a fairly rapid process (occurring approximately 100 minutes after activity) that is independent of protein synthesis. NMDAR activity reduces phosphorylation of β-catenin at tyr-654, thereby inhibiting N-cadherin endocytosis and facilitating surface retention and expression. Surface expression is also regulated via protocadherin-mediated adhesion. Protocadherin-alpha and protocadherin-gamma interact to form a protein complex that enhances the surface expression of each cadherin subtype. Cadherin expression is also regulated by activity-induced internalization, which occurs much later than surface stabilization (an average of 4 hours after the stimulus). Internalization is dependent on protein synthesis, and p120 catenin proteins (p120ctn) are implicated in the turnover, degradation and ‘clustering’ of cadherins into the adhesive junctions at the synapse. P120 ctn proteins are thought to either inhibit endocytosis of neural cadherins, or act at the cell surface to control cadherin turnover. Down-regulation of p120 ctn leads to greater cadherin endocytosis and prevents adhesion between the pre and post-synaptic neuron. Such evidence strongly suggests that p120 is necessary for cadherin stability. Binding and signaling Intracellular binding partners β-catenin localizes reserve pool vesicles (RPVs) at presynaptic sites. The deletion of β-catenin in vivo results in a decrease in the number of RPVs localized in the synaptic site and an increase in RPVs dispersed along the axon. Moreover, RPVs were unresponsive to continuous trains of stimulation of the presynaptic neuron in B-catenin knockouts. This effect of B-catenin is independent of cadherin-mediated adhesion, and is instead modulated by PDZ binding proteins such as Veli to cadherin. Additionally, BDNF/TrkB signaling leads to the phosphorylation of β-catenin at its Y654