The Molecular Basis of Destabilization of Synapses as a Factor of Structural Plasticity

Within the framework of ideas about structural plasticity as the basis of long-term memory it has been proven that destabilization of the molecular complex that supports the existing state of the synapse is necessary to begin the consolidation process. This complex consists of proteins of the extracellular matrix, including cell adhesion molecules and transsynaptic proteins, as well as skeletal, scaffold, and anchoring proteins that form the basis for integration and maintenance of signaling and regulatory proteins. We review the experimental data on the importance of destabilization of synapses for efficient maintenance of long-term potentiation (LTP). We demonstrate that induction of structural modifications depends on the composition of NMDA receptors, which are closely related to destabilization of proteins of the cytoskeleton. It is suggested that the interaction of CAMKII and the intracellular domain of NMDA2B receptors is necessary for destabilization and activation of synaptogenesis not only in early ontogeny but also in adult animals, whereas its substitution for the NMDA2A subunit promotes stabilization of synapses. The key role of proteolysis in long-term plasticity and destabilization of synapses is discussed.