title: Dynamic impact of temporal context of Ca²⁺ signals on inhibitory synaptic plasticity.
abstract: Neuronal activity-dependent synaptic plasticity, a basis for learning and memory, is tightly correlated with the pattern of increase in intracellular Ca(2+) concentration ([Ca(2+)](i)). Here, using combined application of electrophysiological experiments and systems biological simulation, we show that such a correlation dynamically changes depending on the context of [Ca(2+)](i) increase. In a cerebellar Purkinje cell, long-term potentiation of inhibitory GABA(A) receptor responsiveness (called rebound potentiation; RP) was induced by [Ca(2+)](i) increase in a temporally integrative manner through sustained activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). However, the RP establishment was canceled by coupling of two patterns of RP-inducing [Ca(2+)](i) increase depending on the temporal sequence. Negative feedback signaling by phospho-Thr305/306 CaMKII detected the [Ca(2+)](i) context, and assisted the feedforward inhibition of CaMKII through PDE1, resulting in the RP impairment. The [Ca(2+)](i) context-dependent dynamic regulation of synaptic plasticity might contribute to the temporal refinement of information flow in neuronal networks.
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku , Kyoto, 606-8502, Japan. kawaguchi@neurosci.biophys
authors.forename: Shin-Ya
authors.initials: SY
authors.lastname: Kawaguchi
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nagasaki
authors.forename: Tomoo
authors.initials: T
authors.lastname: Hirano
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000378:metabolism; D025461:Feedback, Physiological; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D008959:Models, Neurological; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011689:Purkinje Cells / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism
chemical_list: D050505:Mutant Proteins; D011963:Receptors, GABA-A; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1