Modulatory effects of dopamine on the excitability of the neural networks in the rat prefrontal cortex.

在大鼠内侧前额叶皮层（mPFC）第V层锥体细胞观察了5-羟色胺（5-HT）、去甲肾上腺素（NA）、多巴胺（DA）和M受体激动剂卡巴胆碱（CCh）对电压阶跃诱发的外向后超极化电流（AHP）的影响<mAHP><sAHP>。在体外进行全细胞电压钳记录，以定量测量I_<mAHP>和I_<sAHP>，并检查它们与激动剂存在下的尖峰频率适应的功能联系。CCh、5-HT和NA均降低I_<sAHP>和锋电位适应，并且在某些细胞中，<sAHP>缓慢内向电流（I_）取代了I_，导致<sADP>缓慢后去极化（sADP），而DA尽管在一定浓度范围内对I_的抑制作用相当，但未能增加频率<sAHP>。为了检测神经调节剂激动剂对I_2的作用是否具有相加作用<sAHP>，我们研究了两种激动剂（5-HT+NA，CCh+5-HT和NA+CCh）在30 μM浓度下的联合作用，发现CCh对慢后极化电流的作用具有相加作用，这可能是通过抑制I_2<sAHP>和产生I_2两种途径实现的<sADP>。这些结果表明，神经调制剂在I调制和尖峰频率适应之间的联系中具有不同的作用<sAHP>，它们对强兴奋后的慢后电流具有相加作用，从而调节大鼠mPFC输出细胞的重复放电特性。

The effects of 5-hydroxytryptamine (5-HT), noradrenaline (NA), dopamine (DA) and the muscarinic receptor agonist carbachol (CCh)on the voltage step-induced outward currents underlying afterhyperpolarization (AHP),consisting of a medium (I_<mAHP>) and slow (I_<sAHP>) component, were investigated in layer V pyramidal cells of the rat medial prefrontal cortex (mPFC). Whole-cell voltage clamp recordings were performed in vitro to quantitatively measure I_<mAHP> and I_<sAHP> and to examine their functional link to spike-frequency adaptation in the presence of agonists. CCh, 5-HT and NA all reduced the I_<sAHP> and the spike adaptation, and, in some cells, replaced the I_<sAHP> by the slow inward currents (I_<sADP>) underlying the slow afterdepolarization (sADP).DA, however, failed to increase the frequency despite its comparable inhibition of the I_<sAHP> over a range of concentrations. In order to test the neuromodulator agonists to see if they have additive actions on the I_<sAHP>, the effects of co-application of two agonists that increased spike-frequency, 5-HT+NA, CCh+5-HT and NA+CCh, all at the concentration 30 μM were examined.Specific combinations that included CCh showed additive effects on the slow afterpolarization currents, possibly via both inhibition of I_<sAHP> and generation of I_<sADP>. These findings suggest that neuromodulators have differential effects on the link between the I_<sAHP> modulation and spike-frequency adaptation, and that they could exert additive effects on the slow aftercurrents following a strong excitation and, therefore, regulate the repetitive firing properties of the output cells of the rat mPFC.