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Neurobiological model of stimulated dopamine neurotransmission to interpret fast-scan cyclic voltammetry data

机译：刺激多巴胺神经传递的神经生物学模型解释快速扫描循环伏安数据

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Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can assess real-time in vivo dopamine (DA) concentration changes to study the kinetics of DA neuro-transmission. Electrical stimulation of dopaminergic (DAergic) pathways can elicit FSCV DA responses that largely reflect a balance of DA release and reuptake. Interpretation of these evoked DA responses requires a framework to discern the contribution of DA release and reuptake. The current, widely implemented interpretive framework for doing so is the Michaelis-Menten (M-M) model, which is grounded on two assumptions- (1) DA release rate is constant during stimulation, and (2) DA reuptake occurs through dopamine transporters (DAT) in a manner consistent with M-M enzyme kinetics. Though the M-M model can simulate evoked DA responses that rise convexly, response types that predominate in the ventral striatum, the M-M model cannot simulate dorsal striatal responses that rise concavely. Based on current neurotransmission principles and experimental FSCV data, we developed a novel, quantitative, neurobiological framework to interpret DA responses that assumes DA release decreases exponentially during stimulation and continues post-stimulation at a diminishing rate. Our model also incorporates dynamic M-M kinetics to describe DA reuptake as a process of decreasing reuptake efficiency. We demonstrate that this quantitative, neurobiological model is an extension of the traditional M-M model that can simulate heterogeneous regional DA responses following manipulation of stimulation duration, frequency, and DA pharmacology. The proposed model can advance our interpretive framework for future in vivo FSCV studies examining regional DA kinetics and their alteration by disease and DA pharmacology. (C) 2015 Elsevier B.V. All rights reserved.
机译：快速扫描循环伏安法（FSCV）是一种电化学方法，可以评估实时体内多巴胺（DA）浓度变化，以研究DA神经传递的动力学。多巴胺能（DAergic）途径的电刺激可引起FSCV DA反应，这在很大程度上反映了DA释放和再摄取的平衡。对这些诱发的DA应答的解释需要一个框架来识别DA释放和再摄取的贡献。当前广泛使用的解释框架是Michaelis-Menten（MM）模型，该模型基于两个假设：（1）DA在刺激过程中的释放速率恒定，（2）DA通过多巴胺转运蛋白（DAT）重新摄取）的方式与MM酶动力学一致。尽管M-M模型可以模拟诱发的DA凸起凸出的反应，但反应类型主要在腹侧纹状体中，但是M-M模型不能模拟凹入的背面纹状体反应。基于当前的神经传递原理和实验性FSCV数据，我们开发了一种新颖的，定量的，神经生物学的框架来解释DA反应，该假设假定DA释放在刺激过程中呈指数下降，并在刺激后继续以递减的速率进行。我们的模型还结合了动态M-M动力学来描述DA重摄取是降低重摄取效率的过程。我们证明了这种定量的神经生物学模型是传统M-M模型的扩展，该模型可以模拟刺激持续时间，频率和DA药理作用后的异质区域DA反应。所提出的模型可以为今后的体内FSCV研究提供便利，以研究区域DA动力学及其因疾病和DA药理作用而引起的变化，从而为我们的解释框架提供了依据。 （C）2015 Elsevier B.V.保留所有权利。

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