Binding of Filamentous Actin to CaMKII as Potential Regulation Mechanism of Bidirectional Synaptic Plasticity by β CaMKII in Cerebellar Purkinje Cells

• Published in: Scientific reports Vol. 10; no. 1; p. 9019
• Main Authors: Pinto, Thiago M., Schilstra, Maria J., Roque, Antonio C., Steuber, Volker
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.06.2020; Nature Publishing Group
• Subjects: 631/114/116/2392; 631/114/2391; Actin; Actins - metabolism; Animals; Ca2+/calmodulin-dependent protein kinase II; Calcineurin; Calcineurin - metabolism; Calcium-binding protein; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism; Calmodulin; Cerebellar Cortex - cytology; Cerebellar Cortex - physiology; Cerebellar plasticity; Cerebellum; Computer applications; Dephosphorylation; Functional plasticity; Humanities and Social Sciences; Kinases; Long-term depression; Long-term potentiation; Long-Term Potentiation - physiology; Long-Term Synaptic Depression - physiology; Mice, Knockout; Models, Biological; multidisciplinary; Neuronal Plasticity - physiology; Phosphorylation; Protein phosphatase; Purkinje cells; Purkinje Cells - cytology; Purkinje Cells - physiology; Receptors, AMPA - metabolism; Science; Science (multidisciplinary); Synaptic depression; Synaptic plasticity; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-65870-9

Calcium-calmodulin dependent protein kinase II (CaMKII) regulates many forms of synaptic plasticity, but little is known about its functional role during plasticity induction in the cerebellum. Experiments have indicated that the β isoform of CaMKII controls the bidirectional inversion of plasticity at parallel fibre (PF)-Purkinje cell (PC) synapses in cerebellar cortex. Because the cellular events that underlie these experimental findings are still poorly understood, we developed a simple computational model to investigate how β CaMKII regulates the direction of plasticity in cerebellar PCs. We present the first model of AMPA receptor phosphorylation that simulates the induction of long-term depression (LTD) and potentiation (LTP) at the PF-PC synapse. Our simulation results suggest that the balance of CaMKII-mediated phosphorylation and protein phosphatase 2B (PP2B)-mediated dephosphorylation of AMPA receptors can determine whether LTD or LTP occurs in cerebellar PCs. The model replicates experimental observations that indicate that β CaMKII controls the direction of plasticity at PF-PC synapses, and demonstrates that the binding of filamentous actin to CaMKII can enable the β isoform of the kinase to regulate bidirectional plasticity at these synapses.