van der Velden Luuk, Vinck Martin A, Werkman Taco R, Wadman Wytse J
Center for Neuroscience, University of Amsterdam, Amsterdam, Netherlands.
Ernst Strüngmann Institute for Neuroscience in Cooperation With Max Planck Society, Frankfurt am Main, Germany.
Front Integr Neurosci. 2019 Jun 25;13:20. doi: 10.3389/fnint.2019.00020. eCollection 2019.
Micro Electrode Arrays were used to simultaneously record spontaneous extracellular action potentials from 10 to 30 dopamine neurons in acute brain slices from the lateral Ventral Tegmental Area (VTA) of the rat. The spike train of an individual neuron was used to characterize the firing pattern: firing rate, firing irregularity and oscillation frequency. Functional connectivity between a pair of neurons was quantified by the Paired Phase Consistency (PPC), taking the oscillation frequency as reference. Under baseline conditions the PPC was significantly different from zero and 42 of the 386 pairs of VTA neurons showed significant coupling. Fifty percent of the recorded dopamine neurons were part of the coupled VTA network. Raising extracellular potassium from 3.5 to 5 mM increased the mean firing rate of the dopamine neurons by 45%. The same increase could be induced by bath application of 300 μm glutamate. High potassium reduced the PPC, but it did not change during the glutamate application. Our findings imply that manipulating excitability has distinct and specific consequences for functional connectivity in the VTA network that cannot be directly predicted from the changes in neuronal firing rates. Functional connectivity reflects the spatial organization and synchronization of the VTA output and thus represents a unique element of the message that is sent to the mesolimbic projection area. It adds a dimension to pharmacological manipulation of the VTA micro circuit that might help to understand the pharmacological (side) effects of e.g., anti-psychotic drugs.
微电极阵列被用于同时记录来自大鼠腹侧被盖区（VTA）外侧急性脑片上10至30个多巴胺能神经元的自发细胞外动作电位。单个神经元的脉冲序列用于表征放电模式：放电频率、放电不规则性和振荡频率。以振荡频率为参考，通过配对相位一致性（PPC）对一对神经元之间的功能连接性进行量化。在基线条件下，PPC显著不同于零，386对VTA神经元中的42对显示出显著的耦合。记录的多巴胺能神经元中有50%是耦合的VTA网络的一部分。将细胞外钾浓度从3.5 mM提高到5 mM可使多巴胺能神经元的平均放电频率增加45%。通过浴加300 μM谷氨酸也可诱导相同的增加。高钾降低了PPC，但在应用谷氨酸期间其未发生变化。我们的研究结果表明，操纵兴奋性对VTA网络中的功能连接性具有独特且特定的影响，而这些影响无法从神经元放电频率的变化中直接预测。功能连接性反映了VTA输出的空间组织和同步性，因此代表了发送到中脑边缘投射区域的信息的一个独特元素。它为VTA微电路的药理学操纵增加了一个维度，这可能有助于理解例如抗精神病药物的药理学（副作用）。
