title: Opposite regulation of inhibitory synaptic plasticity by α and β subunits of Ca(2+)/calmodulin-dependent protein kinase II.
abstract: Induction of several forms of synaptic plasticity, a cellular basis for learning and memory, depends on the activation of Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII). CaMKII acts as a holoenzyme consisting of α and β subunits (α- and βCaMKII). However, it remains elusive how the subunit composition of a CaMKII holoenzyme affects its activation and hence synaptic plasticity. We addressed this issue by focusing on long-term potentiation (LTP) at inhibitory synapses on cerebellar Purkinje neurons (PNs) (called rebound potentiation, RP). The contribution of each subunit to RP was examined by selective knock-down or overexpression of that subunit. Electrophysiological recording from a rat cultured PN demonstrated that βCaMKII is essential for RP induction, whereas αCaMKII suppresses it. Thus, RP was negatively regulated due to the greater relative abundance of αCaMKII compared to βCaMKII, suggesting a critical role of CaMKII subunit composition in RP. The higher affinity of βCaMKII to Ca(2+)/CaM compared with αCaMKII was responsible for the predominant role in RP induction. Live-cell imaging of CaMKII activity based on the Förster resonance energy transfer (FRET) technique revealed that βCaMKII enrichment enhances the total CaMKII activation upon a transient conditioning depolarization. Taken together, these findings clarified that α- and βCaMKII oppositely regulate CaMKII activation, controlling the induction of inhibitory synaptic plasticity in a PN, which might contribute to the adaptive information processing of the cerebellar cortex.
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nagasaki
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto, 606-8502, Japan Graduate School of Brain Science, Doshisha University, Kizugawa-shi, Kyoto, 619-0025, Japan skawaguc@mail.doshisha.ac.jp.
authors.forename: Shin-ya
authors.initials: SY
authors.lastname: Kawaguchi
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D053444:Inhibitory Postsynaptic Potentials; D017774:Long-Term Potentiation; D008297:Male; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D011689:Purkinje Cells / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D021122:Protein Subunits; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2