Wightman R Mark, Heien Michael L A V, Wassum Kate M, Sombers Leslie A, Aragona Brandon J, Khan Amina S, Ariansen Jennifer L, Cheer Joseph F, Phillips Paul E M, Carelli Regina M
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3290, USA.
Eur J Neurosci. 2007 Oct;26(7):2046-54. doi: 10.1111/j.1460-9568.2007.05772.x. Epub 2007 Sep 14.
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 approximately 50 nm. 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.
完整大脑中的许多单个神经元以随机模式放电,这些模式源于它们与所构成的神经回路之间的相互作用。然而,由于适用于监测微米尺度下亚秒级化学事件的传感器直到最近才出现,这些放电模式所引发的化学通讯尚未得到表征。在此,我们采用伏安传感器技术结合主成分回归来研究清醒且不受束缚的大鼠伏隔核(NAc)中多巴胺浓度的动态变化。该传感器具有亚毫米尺寸,并提供高时间分辨率(0.1秒)。在选定位置检测到自发的多巴胺瞬态浓度变化,瞬时浓度达到约50纳米。在其他位置,尽管多巴胺可用于释放,如多巴胺能神经元电激活后细胞外多巴胺增加所示,但未检测到瞬态变化。在出现多巴胺浓度瞬变的位点,可卡因的摄取抑制作用增强了快速瞬变的频率和幅度,同时也导致细胞外多巴胺更缓慢地增加。在不支持持续瞬态活动的位点,这些效应基本不存在。这些发现揭示了伏隔核内多巴胺传递中出乎意料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情况。