A model of NMDA receptor-mediated activity in dendrites of hippocampal CA1 pyramidal neurons.
A model of NMDA receptor-mediated activity in dendrites of hippocampal CA1 pyramidal neurons.
复制标题
海马 CA1 锥体神经元树突中 NMDA 受体介导的活性模型。
DOI：
10.1152/jn.1992.68.6.2248
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发表时间：
1992
影响因子：
2.5
通讯作者：
Shepherd,GM
中科院分区：
文献类型：
--
作者：
Pongracz,F;Poolos,NP;Kocsis,JD;Shepherd,GM
1. 利用计算模型研究了 CA1 海马锥体细胞 NMDA（N-甲基-D-天冬氨酸）受体介导的突触激活电导在短期兴奋性变化中的作用。模型参数基于树突和体细胞的实验记录以及之前的海马模拟。 CA1 神经元的表示包括 NMDA 和非 NMDA 兴奋性树突突触、树突和体细胞抑制、五种内在膜电导，以及提供活性依赖性的细胞内和细胞外离子浓度变化。 2. 该模型模拟了实验记录的体细胞电位和树突电位。特征性 CA1 去极化后尖峰是树突电荷纵向扩散、缓慢 Ca(2+) 依赖性 K+ 电导重新激活、缓慢突触过程（NMDA 依赖性去极化和 γ-氨基丁酸介导的超极化电流）的结果，并且对细胞外钾积累敏感。发现钙电流对于产生去极化后的尖峰不太重要。 3. 重复活动受到 NMDA 介导的突触电导的累积激活、抑制性突触反应的频率依赖性抑制以及钾逆转电位的变化的影响。 NMDA 受体激活产生兴奋性突触后电位 (EPSP) 的短暂增强。 EPSP增强的频率依赖性与实验数据相似，在10 Hz附近达到最大值。 4.虽然本模型没有树突棘隔室，但在树突膜细胞内表面附近的有限空间中模拟了Ca2+积累。模拟表明，即使在没有 Ca2+ 尖峰的情况下，NMDA 操作的突触电流的 Ca2+ 成分也可能是增加膜下区域 Ca2+ 浓度的重要因素。 5. 细胞外K+浓度的升高增强了重复活动期间树突突触的反应，并导致细胞内Ca2+水平增加。树突兴奋性的增加部分是由 NMDA 受体介导的电导介导的。 6. 阻断树突中 Ca(2+) 敏感的 K+ 电导会增加 EPSP 的大小，从而促进树突和体细胞尖峰活动并增加 [Ca2+]i。 NMDA 受体介导的电导作为该机制中的放大成分出现，由相对去极化的膜电位激活。 7. 结果表明，树突状 NMDA 受体凭借其电压依赖性，可以与许多电压敏感电导相互作用，以增加突触重复激活期间的树突状兴奋反应。这些发现支持实验结果，表明 NMDA 受体介导的电导与 CA1 海马锥体神经元的短期反应可塑性有关。
1. The role of synaptic activation of NMDA (N-methyl-D-aspartate) receptor-mediated conductances on CA1 hippocampal pyramidal cells in short-term excitability changes was studied with the use of a computational model. Model parameters were based on experimental recordings from dendrites and somata and previous hippocampal simulations. Representation of CA1 neurons included NMDA and non-NMDA excitatory dendritic synapses, dendritic and somatic inhibition, five intrinsic membrane conductances, and provision for activity-dependent intracellular and extracellular ion concentration changes. 2. The model simulated somatic and dendritic potentials recorded experimentally. The characteristic CA1 spike afterdepolarization was a consequence of the longitudinal spread of dendritic charge, reactivation of slow Ca(2+)-dependent K+ conductances, slow synaptic processes (NMDA-dependent depolarizing and gamma-aminobutyric acid-mediated hyperpolarizing currents) and was sensitive to extracellular potassium accumulation. Calcium currents were found to be less important in generating the spike afterdepolarization. 3. Repetitive activity was influenced by the cumulative activation of the NMDA-mediated synaptic conductances, the frequency-dependent depression of inhibitory synaptic responses, and a shift in the potassium reversal potential. NMDA receptor activation produced a transient potentiation of the excitatory postsynaptic potential (EPSP). The frequency dependence of EPSP potentiation was similar to the experimental data, reaching a maximal value near 10 Hz. 4. Although the present model did not have compartments for dendritic spines, Ca2+ accumulation was simulated in a restricted space near the intracellular surface of the dendritic membrane. The simulations demonstrated that the Ca2+ component of the NMDA-operated synaptic current can be a significant factor in increasing the Ca2+ concentration at submembrane regions, even in the absence of Ca2+ spikes. 5. Elevation of the extracellular K+ concentration enhanced the dendritic synaptic response during repetitive activity and led to an increase in intracellular Ca2+ levels. This increase in dendritic excitability was partly mediated by NMDA receptor-mediated conductances. 6. Blockade of Ca(2+)-sensitive K+ conductances in the dendrites increased the size of EPSPs leading to a facilitation of dendritic and somatic spike activity and increased [Ca2+]i. NMDA receptor-mediated conductances appeared as an amplifying component in this mechanism, activated by the relatively depolarized membrane potential. 7. The results suggest that dendritic NMDA receptors, by virtue of their voltage-dependency, can interact with a number of voltage-sensitive conductances to increase the dendritic excitatory response during periods of repetitive synaptic activation. These findings support experimental results that implicate NMDA receptor-mediated conductances in the short-term response plasticity of the CA1 hippocampal pyramidal neuron.