kn-62 and 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic-acid

Long-term potentiation (LTP) is accompanied by dendritic spine growth and changes in the composition of the postsynaptic density (PSD). We find that activity-dependent growth of apical spines of CA1 pyramidal neurons is accompanied by destabilization of the PSD that results in transient loss and rapid replacement of PSD-95 and SHANK2. Signaling through PSD-95 is required for activity-dependent spine growth and trafficking of SHANK2. N-terminal PDZ and C-terminal guanylate kinase domains of PSD-95 are required for both processes, indicating that PSD-95 coordinates multiple signals to regulate morphological plasticity. Activity-dependent trafficking of PSD-95 is triggered by phosphorylation at serine 73, a conserved calcium/calmodulin-dependent protein kinase II (CaMKII) consensus phosphorylation site, which negatively regulates spine growth and potentiation of synaptic currents. We propose that PSD-95 and CaMKII act at multiple steps during plasticity induction to initially trigger and later terminate spine growth by trafficking growth-promoting PSD proteins out of the active spine.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Animals, Newborn; Dendritic Spines; Disks Large Homolog 4 Protein; Electric Stimulation; Enzyme Inhibitors; Excitatory Amino Acid Antagonists; Glutamates; Green Fluorescent Proteins; Hippocampus; Indoles; Intracellular Signaling Peptides and Proteins; Long-Term Potentiation; Membrane Proteins; Nerve Tissue Proteins; Neuronal Plasticity; Neurons; Organ Culture Techniques; Patch-Clamp Techniques; Phosphorylation; Piperazines; Point Mutation; Protein Structure, Tertiary; Protein Transport; Rats; Rats, Sprague-Dawley; Serine; Time Factors