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

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

Modeling the electric potential across neuronal membranes: the effect of fixed charges on spinal ganglion neurons and neuroblastoma cells.

We present a model for the electric potential profile across the membranes of neuronal cells. We considered the resting and action potential states, and analyzed the influence of fixed charges of the membrane on its electric potential, based on experimental values of membrane properties of the spinal ganglion neuron and the neuroblastoma cell. The spinal ganglion neuron represents a healthy neuron, and the neuroblastoma cell, which is tumorous, represents a pathological neuron. We numerically solved the non-linear Poisson-Boltzmann equation for the regions of the membrane model we have adopted, by considering the densities of charges dissolved in an electrolytic solution and fixed on both glycocalyx and cytoplasmic proteins. Our model predicts that there is a difference in the behavior of the electric potential profiles of the two types of cells, in response to changes in charge concentrations in the membrane. Our results also describe an insensitivity of the neuroblastoma cell membrane, as observed in some biological experiments. This electrical property may be responsible for the low pharmacological response of the neuroblastoma to certain chemotherapeutic treatments.