Abstract
Historically, long-term potentiation (LTP) and long-term depression (LTD), the best-characterized forms of long-term synaptic plasticity, are viewed as experience-dependent and input-specific processes. However, cumulative experimental and theoretical data have demonstrated that LTP and LTD can promote compensatory alterations in non-stimulated synapses. In this work, we have developed a computational model of a tridimensional spiny dendritic segment to investigate the role of AMPA receptor (AMPAR) trafficking during synaptic plasticity at specific synapses and its consequences for the populations of AMPAR at nearby synapses. Our results demonstrated that the mechanisms of AMPAR trafficking involved with LTP and LTD can promote heterosynaptic plasticity at non-stimulated synapses. These alterations are compensatory and arise from molecular competition. Moreover, the heterosynaptic changes observed in our model can modulate further activity-driven inductions of synaptic plasticity.
Highlights
Long-term forms of synaptic plasticity are persistent modifications in the efficacy of the synaptic transmission[1]
To investigate the dynamic regulation of AMPA receptor (AMPAR), we developed a tridimensional mesh in CellBlender/MCell[18,19,20] to simulate a small dendritic segment containing 5 dendritic spines (Fig. 1A,B)
Our results showed that the simulation of enzLTP inside a single dendritic spine increased its population of synaptic AMPARs (Fig. 3C)
Summary
Long-term forms of synaptic plasticity are persistent modifications in the efficacy of the synaptic transmission[1]. The structure of the dendritic spines confines the molecules involved with the excitatory postsynaptic transmission and synaptic plasticity[2,4] and contributes to the notion that LTP and LTD are input-specific[5]. At the synapses between pyramidal CA3 and CA1 hippocampal neurons, LTP involves an increase in the number of synaptic AMPARs in an activity-dependent manner[14]. LTD requires the reduction of synaptic AMPAR clusters[14] It is unclear whether changes in the number of AMPARs at one synapse affect adjacent synapses in compensatory manners. We used the model to investigate whether activity-dependent changes in the population of AMPARs of specific dendritic spines regulate the synaptic strength of non-stimulated vicinal synapses. Our results revealed that the mechanisms of AMPAR trafficking can promote heterosynaptic plasticity and, contribute to the stabilization of the neuronal activity during occurrences of synaptic plasticity
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