Computational study of NMDA conductance and cortical oscillations in schizophrenia.
Computational study of NMDA conductance and cortical oscillations in schizophrenia.
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DOI：
10.3389/fncom.2014.00133
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发表时间：
2014
影响因子：
3.2
通讯作者：
Cho RY
中科院分区：
文献类型：
--
作者：
Kirli KK;Ermentrout GB;Cho RY
n -甲基- d -天冬氨酸（NMDA）受体功能障碍与精神分裂症的病理生理有关。该疾病还以伽马振荡干扰为特征，可以使用听觉皮层带动范式以精确的频率特异性进行评估。这项计算研究探讨了突触NMDA功能减退如何引起网络水平的振荡缺陷，并以带动范式为索引。我们建立了一个由锥体细胞和快速尖峰中间神经元（FSI）组成的局部皮层回路的计算模型，该模型结合了NMDA、α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）和γ-氨基丁酸（GABA）突触动力学。我们评估了不同的NMDA电导对FSIs和锥体细胞的影响，以及AMPA与NMDA的比值。我们还研究了在广泛的夹带频率范围内作为NMDA电导函数的差异效应。NMDA在fsi细胞上的电导变化与网络γ呈倒u关系，而NMDA在锥体细胞上的电导则具有更单调的关系。不同的NMDA和AMPA在fsi上的电导证明了AMPA在伽马生成中的必要性，而NMDA受体具有调节作用。最后，减少NMDA对FSI的电导和改变刺激输入频率可以重现在精神分裂症研究中观察到的伽马范围（~40 Hz）的特定减少。我们的计算研究表明，NMDA传导到fsi上的减少可以重现类似于在精神分裂症研究中报道的伽马范围内周期性刺激的干扰。这些发现为特定细胞水平的紊乱如何在精神分裂症中引起回路水平的病理生理紊乱提供了一个机制解释。
N-methyl-D-aspartate (NMDA) receptor hypofunction has been implicated in the pathophysiology of schizophrenia. The illness is also characterized by gamma oscillatory disturbances, which can be evaluated with precise frequency specificity employing auditory cortical entrainment paradigms. This computational study investigates how synaptic NMDA hypofunction may give rise to network level oscillatory deficits as indexed by entrainment paradigms. We developed a computational model of a local cortical circuit with pyramidal cells and fast-spiking interneurons (FSI), incorporating NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA), and γ-aminobutyric acid (GABA) synaptic kinetics. We evaluated the effects of varying NMDA conductance on FSIs and pyramidal cells, as well as AMPA to NMDA ratio. We also examined the differential effects across a broad range of entrainment frequencies as a function of NMDA conductance. Varying NMDA conductance onto FSIs revealed an inverted-U relation with network gamma whereas NMDA conductance onto the pyramidal cells had a more monotonic relationship. Varying NMDA vs. AMPA conductance onto FSIs demonstrated the necessity of AMPA in the generation of gamma while NMDA receptors had a modulatory role. Finally, reducing NMDA conductance onto FSI and varying the stimulus input frequency reproduced the specific reductions in gamma range (~40 Hz) as observed in schizophrenia studies. Our computational study showed that reductions in NMDA conductance onto FSIs can reproduce similar disturbances in entrainment to periodic stimuli within the gamma range as reported in schizophrenia studies. These findings provide a mechanistic account of how specific cellular level disturbances can give rise to circuitry level pathophysiologic disturbance in schizophrenia.
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影响因子：
5.3
作者：
Green, Michael F.
通讯作者：
Green, Michael F.
影响因子：
--
作者：
Izhikevich, EM
通讯作者：
Izhikevich, EM
影响因子：
3
作者：
Basar-Eroglu, Canan;Brand, Andreas;Schmiedt, Christina
通讯作者：
Schmiedt, Christina
DOI：
10.1073/pnas.0609440103
发表时间：
2006-12-26
影响因子：
11.1
作者：
Cho, R. Y.;Konecky, R. O.;Carter, C. S.
通讯作者：
Carter, C. S.
DOI：
10.1111/j.1460-9568.2012.08071.x
发表时间：
2012-07
期刊：
The European journal of neuroscience
影响因子：
--
作者：
Kömek K;Bard Ermentrout G;Walker CP;Cho RY
通讯作者：
Cho RY