How Spines Cross-Talk: Compartmental Model of Heterosynaptic Plasticity

This study addresses the fundamental principle of inter-synaptic interactions in synaptic cross-talk through homosynaptic and heterosynaptic plasticity by studying the intrinsic calcium signaling dynamics in spines. Beyond the calcium influx into synapse through voltage gated calcium channels (VGCCs) and N-methyl-D-aspartate (NNMDA) receptors, the function of calcium released from internal store in mediating inter-synaptic cross-talk has barely been modeled. This work investigates how different sources of calcium contribute to inter-synaptic cross-talk and synaptic clustering. Based on experimental observations, we developed a mathematical model in one dimensional system with uniform distribution of spines with the connected dendrite. We modeled the biophysical process of calcium induced calcium release (CICR) in the dendritic smooth endoplasmic reticulum (SER). Our model compared distinct roles of calcium diffusion, back propagated action potentials (bAPs) and CICR played in synaptic clustering and inter-synaptic cross-talk. The simulation result demonstrated that calcium signal extruded from spine into dendrite requires amplification by CICR before invading neighboring spines to induce plasticity. Our model predicted that initial calcium concentration in SER may discriminate between different types of neuronal activity and induce completely different synaptic potentiation and depression.