Synergy of AMPA and NMDA Receptor Currents in Dopaminergic Neurons: A Modeling Study.
Synergy of AMPA and NMDA Receptor Currents in Dopaminergic Neurons: A Modeling Study.
复制标题
DOI：
10.3389/fncom.2016.00048
复制
发表时间：
2016
影响因子：
3.2
通讯作者：
Kuznetsov A
中科院分区：
文献类型：
--
作者：
Zakharov D;Lapish C;Gutkin B;Kuznetsov A
多巴胺能神经元有两种放电模式：低频强直和高频爆发。爆发内的高频放电归因于NMDA，而不是AMPA受体激活。在我们的DA神经元模型中，无论是生物物理的还是抽象的，NMDA受体电流都可以显著增加它们的放电频率，而AMPA受体电流不能引起高频活动，并且通常抑制放电。然而，这两种电流都是由谷氨酸受体产生的，因此通常是共同激活的。在这里，我们考虑DA神经元模型中AMPA和NMDA突触输入的综合影响。根据AMPAR和NMDAR电流的电导，观察到不同类型的神经元活动（静息状态、低频或高频放电）。在两个模型中，生物物理和减少，我们表明，发射频率增加更有效地，如果两个受体共同激活某些参数值。特别是，在更定量的生物物理模型中，最大频率比单独使用NMDAR的频率高40%。这种频率增长的动力学机制的相空间演化的框架内解释使用减少模型。简而言之，AMPAR和NMDAR电流都使电压零倾变平，提供频率增加，而只有NMDA防止零倾的完全展开，提供稳健的激发。因此，我们证实了NMDAR在产生高频放电中的主要作用，并得出结论，AMPAR激活进一步显着增加频率。
Dopaminergic (DA) neurons display two modes of firing: low-frequency tonic and high-frequency bursts. The high frequency firing within the bursts is attributed to NMDA, but not AMPA receptor activation. In our models of the DA neuron, both biophysical and abstract, the NMDA receptor current can significantly increase their firing frequency, whereas the AMPA receptor current is not able to evoke high-frequency activity and usually suppresses firing. However, both currents are produced by glutamate receptors and, consequently, are often co-activated. Here we consider combined influence of AMPA and NMDA synaptic input in the models of the DA neuron. Different types of neuronal activity (resting state, low frequency, or high frequency firing) are observed depending on the conductance of the AMPAR and NMDAR currents. In two models, biophysical and reduced, we show that the firing frequency increases more effectively if both receptors are co-activated for certain parameter values. In particular, in the more quantitative biophysical model, the maximal frequency is 40% greater than that with NMDAR alone. The dynamical mechanism of such frequency growth is explained in the framework of phase space evolution using the reduced model. In short, both the AMPAR and NMDAR currents flatten the voltage nullcline, providing the frequency increase, whereas only NMDA prevents complete unfolding of the nullcline, providing robust firing. Thus, we confirm a major role of the NMDAR in generating high-frequency firing and conclude that AMPAR activation further significantly increases the frequency.