Underlying Mechanisms of Cooperativity, Input Specificity, and Associativity of Long-Term Potentiation Through a Positive Feedback of Local Protein Synthesis

Frontiers in Computational Neuroscience
Lijie HaoJinzhi Lei

Abstract

Long-term potentiation (LTP) is a specific form of activity-dependent synaptic plasticity that is a leading mechanism of learning and memory in mammals. The properties of cooperativity, input specificity, and associativity are essential for LTP; however, the underlying mechanisms are unclear. Here, based on experimentally observed phenomena, we introduce a computational model of synaptic plasticity in a pyramidal cell to explore the mechanisms responsible for the cooperativity, input specificity, and associativity of LTP. The model is based on molecular processes involved in synaptic plasticity and integrates gene expression involved in the regulation of neuronal activity. In the model, we introduce a local positive feedback loop of protein synthesis at each synapse, which is essential for bimodal response and synapse specificity. Bifurcation analysis of the local positive feedback loop of brain-derived neurotrophic factor (BDNF) signaling illustrates the existence of bistability, which is the basis of LTP induction. The local bifurcation diagram provides guidance for the realization of LTP, and the projection of whole system trajectories onto the two-parameter bifurcation diagram confirms the predictions obtained from bifurcat...Continue Reading

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Citations

Feb 23, 2020·IUBMB Life·Júlia PinhoRosalina Fonseca
Nov 28, 2020·Frontiers in Neurology·Viviana MucciBruno Burlando
Feb 14, 2021·Neuroscience and Biobehavioral Reviews·Ewa Galaj, Robert Ranaldi
Dec 6, 2021·Current Opinion in Neurology·Viviana MucciCherylea J Browne

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