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

Author(s)

Pinto, Thiago M. ^{[1, 2]} ; Schilstra, Maria J. ^[3] ; Roque, Antonio C. ^[1] ; Steuber, Volker ^[3]

Affiliation

^[1] Univ Sao Paulo, FFCLRP, Dept Fis, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Inst Fed Educ Ciencia & Tecnol Rio de Janeiro, BR-26530060 Nilopolis, RJ - Brazil

^[3] Univ Hertfordshire, Ctr Comp Sci & Informat Res, Hatfield AL10 9AB, Herts - England

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 JUN 2 2020.
• Web of Science Citations: 0

Abstract

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 beta 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 beta 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 beta CaMKII controls the direction of plasticity at PF-PC synapses, and demonstrates that the binding of filamentous actin to CaMKII can enable the beta isoform of the kinase to regulate bidirectional plasticity at these synapses. (AU)

• FAPESP's process: 13/17063-5 - Computational modelling of intracellular signalling pathways and the study of synaptic plasticity induction in the cerebellum
• Grantee: Thiago Matos Pinto
• Support Opportunities: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 13/07699-0 - Research, Innovation and Dissemination Center for Neuromathematics - NeuroMat
• Grantee: Jefferson Antonio Galves
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 15/50122-0 - Dynamic phenomena in complex networks: basics and applications
• Grantee: Elbert Einstein Nehrer Macau
• Support Opportunities: Research Projects - Thematic Grants