Regulation of synaptogenesis and synaptic plasticity by cell adhesion molecules

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Central nervous system (CNS) is adapting to the environment at every moment. The adaptation underlies various phenomena such as learning and memory, and dependence and tolerance to abused drugs. Remodeling of neural network is supposed to provide the basis of CNS adaptation.In this study, we have observed the remodeling of synaptic contacts that connects neural fibers resulting in complex neural networking. Dendritic spine, the postsynaptic structure that receives excitatory synaptic input, was visualized in living hippocampal neurons with a heterologously expressed jellyfish green fluorescent protein (GFP). Spine showed rapid reciprocal movement without an artificial stimulation. By synaptic stimulation triggered by membrane depolarization with high K+ extracellular solution, spine became enlarged as much as 30 %. This results in enlargement of the area involved in chemical neurotransmission, hence enhancing the efficiency of neurotransmission. Accumulation of such a neural stimulation and resultant enlargement may lead to the enhancement of a certain neural pathway.We have also investigated the molecular mechanism of the activity-induced synaptic remodeling : 1)Cadherin (a synaptic cell adhesion molecule) activity is required for the enlargement of spine. 2)Synaptic stimulation enhances N-cadherin activity. 3)Another synaptic cell adhesion molecule, Arcadlin, inhibits N-cadherin adhesiveness, and decreases the number of synapses. 4)Arcadlin drives internalization of N-cadherin by endocytosis. 5)The endocytic signal transduction pathway of Arcadlin/N-cadherin involves p38 MAP kinase.These results were submitted to a high quality scientific journal.