A biophysical model of bidirectional synaptic plasticity: Dependence on AMPA and NMDA receptors
A biophysical model of bidirectional synaptic plasticity: Dependence on AMPA and NMDA receptors
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DOI：
10.1073/pnas.201404598
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发表时间：
2001-10-23
影响因子：
11.1
通讯作者：
Shouval, HZ
中科院分区：
文献类型：
--
作者：
Castellani, GC;Quinlan, EM;Shouval, HZ
在大脑的许多区域，包括哺乳动物皮质，突触强度的活动依赖性变化的幅度和方向取决于突触前刺激的频率（突触可塑性）以及这些突触的活动历史（化塑性）。我们基于长期突触增强（LTP）和长期突触抑制（LTD）与α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚基蛋白GluR1位点的磷酸化/去磷酸化相关的观察，提出了双向突触可塑性的分子机制模型。该模型的主要假设是突触后钙浓度以及随后的钙依赖性蛋白激酶和磷酸酶的激活是诱导 LTP/LTD 的触发因素，并得到了广泛的实验支持。由于通过 n-甲基-D-天冬氨酸 (NMDA) 受体的钙流入在 LTP/LTD 的诱导中起着重要作用，因此 NMDA 受体介导的钙流入特性的变化将极大地影响活动依赖性突触可塑性（化生性）。我们证明，实验观察到的化塑性可以通过 NMDA 受体亚基组成和功能的活性依赖性调节来解释。我们的模型产生频率相关的 LTP/LTD 曲线，其具有滑动突触修饰阈值，类似于 Bienenstock、Cooper 和 Munro 理论上提出的并通过实验观察到的阈值。
In many regions of the brain, including the mammalian cortex, the magnitude and direction of activity-dependent changes in synaptic strength depend on the frequency of presynaptic stimulation (synaptic plasticity), as well as the history of activity at those synapses (metaplasticity). We present a model of a molecular mechanism of bidirectional synaptic plasticity based on the observation that longterm synaptic potentiation (LTP) and long-term synaptic depression (LTD) correlate with the phosphorylation/dephosphorylation of sites on the alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit protein GluR1. The primary assumption of the model, for which there is wide experimental support, is that postsynaptic calcium concentration and consequent activation of calcium-dependent protein kinases and phosphatases are the triggers for the induction of LTP/LTD. As calcium influx through the n-methyl-D-aspartate (NMDA) receptor plays a fundamental role in the induction of LTP/LTD, changes in the properties of NMDA receptor-mediated calcium influx will dramatically affect activity-dependent synaptic plasticity (metaplasticity). We demonstrate that experimentally observed metaplasticity can be accounted for by activity-dependent regulation of NMDA receptor subunit composition and function. Our model produces a frequency-dependent LTP/LTD curve with a sliding synaptic modification threshold similar to what has been proposed theoretically by Bienenstock, Cooper, and Munro and observed experimentally.