Mechanisms for multiple activity modes of VTA dopamine neurons.
Mechanisms for multiple activity modes of VTA dopamine neurons.
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DOI：
10.3389/fncom.2015.00095
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发表时间：
2015
影响因子：
3.2
通讯作者：
Gutkin BS
中科院分区：
文献类型：
--
作者：
Oster A;Faure P;Gutkin BS
中脑腹侧节段(VTA)多巴胺能神经元向皮质和皮质下区域发出大量投射，并向靶区广泛释放多巴胺(DA)。DA神经元表现出一系列的活动模式，这些模式在爆发放电的频率和程度上有所不同。重要的是，与同等的紧张性活动模式相比，DA神经元的爆发与DA释放的程度显著相关。在这里，我们介绍了一个单隔室的，基于电导的DA细胞活动的计算模型，该模型捕捉了DA神经元的动力学行为，并检查了DA放电模式背后的多种因素：SK电导的强度，驱动力的大小，以及GABA的抑制。我们的结果表明，低SK电导的神经元在快速放电模式下放电，与猝发放电相关，在进行去极化阻断之前需要更高水平的外加电流。我们继续考虑GABA能抑制对一系列动态类别的DA神经元的作用，发现强烈的GABA抑制抑制了爆发放电。我们的研究表明，SK电导和GABA抑制水平分布的不同可能表明VTA内DA神经元的亚类。我们进一步确认，通过考虑交替的钾动力学，动力学表现出通过去极化阻断终止的爆发模式，类似于在体内观察到的VTA DA神经元和在APamin应用下的黑质致密部(SNC)DA细胞制剂中的那些。此外，我们还考虑了由NMDA启动的或由GABA抑制突然降低所引起的瞬时突发放电事件的产生，即去抑制。
Midbrain ventral segmental area (VTA) dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA) to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst firing. Importantly, DA neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Here, we introduce a single compartmental, conductance-based computational model for DA cell activity that captures the behavior of DA neuronal dynamics and examine the multiple factors that underlie DA firing modes: the strength of the SK conductance, the amount of drive, and GABA inhibition. Our results suggest that neurons with low SK conductance fire in a fast firing mode, are correlated with burst firing, and require higher levels of applied current before undergoing depolarization block. We go on to consider the role of GABAergic inhibition on an ensemble of dynamical classes of DA neurons and find that strong GABA inhibition suppresses burst firing. Our studies suggest differences in the distribution of the SK conductance and GABA inhibition levels may indicate subclasses of DA neurons within the VTA. We further identify, that by considering alternate potassium dynamics, the dynamics display burst patterns that terminate via depolarization block, akin to those observed in vivo in VTA DA neurons and in substantia nigra pars compacta (SNc) DA cell preparations under apamin application. In addition, we consider the generation of transient burst firing events that are NMDA-initiated or elicited by a sudden decrease of GABA inhibition, that is, disinhibition.