Individual and additive effects of neuromodulators on the slow components of afterhyperpolarization currents in layer V pyramidal cells of the rat medial prefrontal cortex
Individual and additive effects of neuromodulators on the slow components of afterhyperpolarization currents in layer V pyramidal cells of the rat medial prefrontal cortex
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DOI：
10.1016/j.brainres.2008.06.098
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发表时间：
2008-09
期刊：
影响因子：
2.9
通讯作者：
Takahiro Satake;H. Mitani;K. Nakagome;K. Kaneko
中科院分区：
文献类型：
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作者：
Takahiro Satake;H. Mitani;K. Nakagome;K. Kaneko
研究了5-羟色胺（5-HT）、去甲肾上腺素（NA）、多巴胺（DA）和毒毒碱受体激动剂恰巴醇（CCh）对大鼠内侧前额叶皮层（mPFC） V层锥体细胞电压阶跃诱导的后超极化（AHP）后向外电流（ImAHP）和IsAHP)的影响。在体外进行全细胞电压钳记录，定量测量imahp和isahp，并检查它们在激动剂存在下与峰值频率适应的功能联系。CCh、5-HT和NA均降低了isahp和尖峰适应，并且在一些细胞中，以慢后去极化（sADP）为基础的慢内向电流（IsADP）取代了isahp。然而，尽管DA在一定浓度范围内对isahpower具有类似的抑制作用，但它未能增加频率。为了检验神经调节剂激动剂对IsAHP是否具有加性作用，在浓度均为30 μM的情况下，观察了增加5-HT+NA、5-HT+CCh和CCh+NA的两种激动剂共同应用对IsAHP的影响。包括CCh在内的特定组合对缓慢后极化电流表现出累加效应，可能是通过抑制isahp和IsADP的产生。这些发现表明，神经调节剂对isahp调节和尖峰频率适应之间的联系具有不同的作用，并且它们可以对强兴奋后的慢后电流施加加性作用，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 (ImAHP) and slow (IsAHP) 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 ImAHPand IsAHPand to examine their functional link to spike-frequency adaptation in the presence of agonists. CCh, 5-HT and NA all reduced the IsAHPand the spike adaptation, and, in some cells, replaced the IsAHPby the slow inward currents (IsADP) underlying the slow afterdepolarization (sADP). DA, however, failed to increase the frequency despite its comparable inhibition of the IsAHPover a range of concentrations. In order to test the neuromodulator agonists to see if they have additive actions on the IsAHP, the effects of co-application of two agonists that increased spike-frequency, 5-HT+NA, 5-HT+CCh and CCh+NA, 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 IsAHPand generation of IsADP. These findings suggest that neuromodulators have differential effects on the link between the IsAHPmodulation 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.