Mathematical modeling of the biphasic dopaminergic response to glucose
Mathematical modeling of the biphasic dopaminergic response to glucose
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DOI：
10.4236/jbise.2011.42020
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发表时间：
2011-02
期刊：
影响因子：
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通讯作者：
Matthias Chung;Britta Göbel;A. Peters;K. Oltmanns;A. Moser
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文献类型：
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作者：
Matthias Chung;Britta Göbel;A. Peters;K. Oltmanns;A. Moser
在这项工作中，我们指定了大脑的潜在元素来感知和调节有机体的能量代谢。我们的数值研究基于神经化学实验，证明了大脑葡萄糖水平和神经元活动之间的双相关联。高、低仿射KATP通道的动力学最有可能在神经元活动中起决定性作用。我们发展了一个耦合的Hodgkin-Huxley模型，描述了投射到尾状核的抑制性GABA能和兴奋性多巴胺能神经元的相互作用行为。我们方法的新颖之处在于，我们包括了GABA能和多巴胺能神经元的突触耦合以及高和低仿射KATP通道的相互作用。两者都是动力学模型所描述的关键机制。模拟表明，我们的新模型与神经化学体外实验是一致的。甚至格列本脲和氨基葡萄糖的实验干预也被我们的新模型重现。我们的结果表明，所考虑的高和低仿射KATP通道的动力学可能是能量感知和能量代谢的全局调节的驱动力，这支持了新的自私脑理论的中心方面。此外，我们的模拟表明，GABA能和多巴胺能神经元的放电频率和模式与它们的神经化学外流有关。
In this work, we specify potential elements of the brain to sense and regulate the energy metabolism of the organism. Our numerical investigations base on neurochemical experiments demonstrating a biphasic association between brain glucose level and neuronal activity. The dynamics of high and low affine KATP channels are most likely to play a decisive role in neuronal activity. We develop a coupled Hodgkin-Huxley model describing the interactive behavior of inhibitory GABAergic and excitatory dopaminergic neurons projecting into the caudate nucleus. The novelty in our approach is that we include the synaptic coupling of GABAergic and dopaminergic neurons as well as the interaction of high and low affine KATP channels. Both are crucial mechanisms described by kinetic models. Simulations demonstrate that our new model is coherent with neurochemical in vitro experiments. Even experimental interventions with glibenclamide and glucosamine are reproduced by our new model. Our results show that the considered dynamics of high and low affine KATP channels may be a driving force in energy sensing and global regulation of the energy metabolism, which supports central aspects of the new Selfish Brain Theory. Moreover, our simulations suggest that firing frequencies and patterns of GABAergic and dopaminergic neurons are correlated to their neurochemical outflow.