Dainauskas Justinas J, Marie Hélène, Migliore Michele, Saudargiene Ausra
Laboratory of Biophysics and Bioinformatics, Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Department of Informatics, Vytautas Magnus University, Kaunas, Lithuania.
Front Synaptic Neurosci. 2023 Mar 15;15:1113957. doi: 10.3389/fnsyn.2023.1113957. eCollection 2023.
Synaptic plasticity is believed to be a key mechanism underlying learning and memory. We developed a phenomenological N-methyl-D-aspartate (NMDA) receptor-based voltage-dependent synaptic plasticity model for synaptic modifications at hippocampal CA3-CA1 synapses on a hippocampal CA1 pyramidal neuron. The model incorporates the GluN2A-NMDA and GluN2B-NMDA receptor subunit-based functions and accounts for the synaptic strength dependence on the postsynaptic NMDA receptor composition and functioning without explicitly modeling the NMDA receptor-mediated intracellular calcium, a local trigger of synaptic plasticity. We embedded the model into a two-compartmental model of a hippocampal CA1 pyramidal cell and validated it against experimental data of spike-timing-dependent synaptic plasticity (STDP), high and low-frequency stimulation. The developed model predicts altered learning rules in synapses formed on the apical dendrites of the detailed compartmental model of CA1 pyramidal neuron in the presence of the GluN2B-NMDA receptor hypofunction and can be used in hippocampal networks to model learning in health and disease.
突触可塑性被认为是学习和记忆的关键机制。我们基于现象学开发了一种基于N-甲基-D-天冬氨酸（NMDA）受体的电压依赖性突触可塑性模型，用于模拟海马CA1锥体神经元上海马CA3-CA1突触的突触修饰。该模型纳入了基于GluN2A-NMDA和GluN2B-NMDA受体亚基的功能，并解释了突触强度对突触后NMDA受体组成和功能的依赖性，而无需明确模拟NMDA受体介导的细胞内钙，后者是突触可塑性的局部触发因素。我们将该模型嵌入到海马CA1锥体细胞的双室模型中，并根据尖峰时间依赖性突触可塑性（STDP）、高频和低频刺激的实验数据对其进行了验证。所开发的模型预测，在存在GluN2B-NMDA受体功能减退的情况下，在CA1锥体神经元详细室模型的顶端树突上形成的突触中，学习规则会发生改变，并且可用于海马网络，以模拟健康和疾病状态下的学习过程。
