Dopamine release is heterogeneous within microenvironments of the rat nucleus accumbens

Dopamine release is heterogeneous within microenvironments of the rat nucleus accumbens
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DOI:
10.1111/j.1460-9568.2007.05772.x
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发表时间:
2007-10-01
影响因子:
3.4
通讯作者:
Carelli, Regina M.
Carelli, Regina M.
中科院分区:
医学3区
文献类型:
--
作者:
Wightman, R. Mark;Heien, Michael L. A. V.;Carelli, Regina M.

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完整大脑中的许多单个神经元以随机模式放电,这些模式是由它们所组成的神经元回路相互作用而产生的。然而,这些激发模式引起的化学通讯尚未得到表征,因为适合监测微米尺寸亚秒级化学事件的传感器最近才出现。在这里,我们采用伏安传感器技术与主成分回归相结合来检查清醒和不受约束的大鼠伏核(NAc)中多巴胺浓度的动态。该传感器具有亚毫米尺寸并提供高时间(0.1 秒)分辨率。在选定的位置,检测到自发的多巴胺瞬时浓度变化,达到类似于 50 的瞬时浓度。在其他位置,即使多巴胺可释放,如多巴胺能神经元电激活后细胞外多巴胺增加所示,瞬变现象也不存在。在发生多巴胺浓度瞬变的部位,可卡因的摄取抑制会增强快速瞬变的频率和幅度,同时也会导致细胞外多巴胺的逐渐增加。不支持持续瞬态活动的站点基本上不存在这些影响。这些发现揭示了 NAc 内多巴胺传输的意想不到的空间和时间异质性,这可能取决于多巴胺神经元特定亚群的放电。
Many individual neurons within the intact brain fire in stochastic patterns that arise from interactions with the neuronal circuits that they comprise. However, the chemical communication that is evoked by these firing patterns has not been characterized because sensors suitable to monitor subsecond chemical events in micron dimensions have only recently become available. Here we employ a voltammetric sensor technology coupled with principal component regression to examine the dynamics of dopamine concentrations in the nucleus accumbens (NAc) of awake and unrestrained rats. The sensor has submillimeter dimensions and provides high temporal (0.1 s) resolution. At select locations spontaneous dopamine transient concentration changes were detected, achieving instantaneous concentrations of similar to 50 . At other locations, transients were absent even though dopamine was available for release as shown by extracellular dopamine increases following electrical activation of dopaminergic neurons. At sites where dopamine concentration transients occur, uptake inhibition by cocaine enhances the frequency and magnitude of the rapid transients while also causing a more gradual increase in extracellular dopamine. These effects were largely absent from sites that did not support ongoing transient activity. These findings reveal an unanticipated spatial and temporal heterogeneity of dopamine transmission within the NAc that may depend upon the firing of specific subpopulations of dopamine neurons.