Multiple effects of dopamine on layer V pyramidal cell excitability in rat prefrontal cortex
Multiple effects of dopamine on layer V pyramidal cell excitability in rat prefrontal cortex
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DOI：
10.1152/jn.2001.86.2.586
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发表时间：
2001-08-01
影响因子：
2.5
通讯作者：
Jaffe, DB
中科院分区：
文献类型：
--
作者：
Gulledge, AT;Jaffe, DB
本文研究了多巴胺（DA）对大鼠内侧前额叶皮层边缘前区V层锥体神经元兴奋性的抑制作用及其机制。在对照条件下，DA抑制动作电位产生（由体细胞电流注入驱动）和输入电阻（R-N）。GABA（A）受体拮抗剂的存在下，阻止DA诱导的动作电位产生的抑郁症，并揭示了一个延迟的兴奋性的增加，持续的实验记录的持续时间，达20分钟后冲洗出DA。与穗产生，去抑制并不影响DA产生的R-N的短暂抑制，表明DA的独立行动的穗产生和R-N。与DA通过GABA能机制减少锥体细胞输出的假设一致，在TTX存在和不存在的情况下，DA增加自发抑制性突触后电流的频率。此外，GABA在体周区域的局部应用模拟了DA对穗产生的抑制作用，而不影响R-N。将荷包牡丹碱局部应用于相同的位置，逆转了浴用DA对穗产生的抑制作用，而对R-N没有影响。由DA的R-N的抑郁症都闭塞和模仿的Na+通道阻滞剂TTX，这表明参与的Na+电导在减少锥体细胞R-N在急性存在的DA。这些数据表明，DA的急性存在降低锥体神经元的兴奋性由两个独立的机制。与此同时，DA触发了兴奋性的延迟和更持久的增加，这部分被突触抑制所掩盖。
The mechanisms underlying the inhibitory effects of dopamine (DA) on layer V pyramidal neuron excitability in the prelimbic region of the rat medial prefrontal cortex were investigated. Under control conditions, DA depressed both action potential generation (driven by somatic current injection) and input resistance (R-N). The presence of GABA(A) receptor antagonists blocked DA-induced depression of action potential generation and revealed a delayed increase in excitability that persisted for the duration of experimental recording, up to 20 min following the wash-out of DA. In contrast to spike generation, disinhibition did not affect the transient depression of R-N produced by DA, suggesting independent actions of DA on spike generation and R-N. Consistent with the hypothesis that DA acts to decrease pyramidal cell output via a GABAergic mechanism, DA increased the frequency of spontaneous inhibitory postsynaptic currents in both the absence and presence of TTX. Furthermore focal application of GABA to a perisomatic region mimicked the inhibitory effect of DA on spike production without affecting R-N. Focal application of bicuculline to the same location reversed the inhibitory effect of bath-applied DA on spike generation, while again having no effect on R-N. The depression of R-N by DA was both occluded and mimicked by the Na+ channel blocker TTX, suggesting the involvement of a Na+ conductance in reducing pyramidal cell R-N during the acute presence of DA. Together these data demonstrate that the acute presence of DA decreases pyramidal neuron excitability by two independent mechanisms. At the same time DA triggers a delayed and longer-lasting increase in excitability that is partially masked by synaptic inhibition.