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

Sci Rep. 2020 Jun 2;10(1):9019. doi: 10.1038/s41598-020-65870-9.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Calcineurin / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism*
  • Cerebellar Cortex / cytology*
  • Cerebellar Cortex / physiology
  • Long-Term Potentiation / physiology
  • Long-Term Synaptic Depression / physiology
  • Mice, Knockout
  • Models, Biological
  • Neuronal Plasticity / physiology*
  • Phosphorylation
  • Purkinje Cells / cytology
  • Purkinje Cells / physiology*
  • Receptors, AMPA / metabolism

Substances

  • Actins
  • Receptors, AMPA
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Camk2b protein, mouse
  • Calcineurin