Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors
Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors
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DOI：
10.1073/pnas.0308280101
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发表时间：
2004-03-02
影响因子：
11.1
通讯作者：
Kandel, ER
中科院分区：
文献类型：
--
作者：
Huang, YY;Simpson, E;Kandel, ER
为了阐明D1受体在内侧前额叶皮层中的作用，我们结合药理学和遗传学操作来研究大鼠和小鼠脑切片中的长时程突触增强（LTP）/长时程突触抑制（LTD）。我们发现，D1拮抗剂SCH 23390选择性地阻断维持，但不诱导LTP在前额叶皮层。相反，D1受体的激活促进了LTP的维持，并且这种作用在杂合D1受体敲除小鼠中受损。低频刺激引起内侧前额叶皮质的短暂抑制。这种抑郁可以通过多巴胺的共同应用转化为LTD。然而，在杂合D1受体敲除小鼠中，多巴胺的共同应用对LTD没有促进作用。这些结果提供了药理学和遗传学证据的作用，D1受体的双向调制的内侧前额叶皮层的突触可塑性。在杂合子敲除小鼠中没有这种调节表明多巴胺受体表达水平的失调可以对前额叶皮层的突触可塑性产生显著影响。
To address the role of D1 receptors in the medial prefrontal cortex, we combined pharmacological and genetic manipulations to examine long-term synaptic potentiation (LTP)/long-term synaptic depression (LTD) in brain slices of rats and mice. We found that the D1 antagonist SCH23390 selectively blocked the maintenance but not the induction of LTP in the prefrontal cortex. Conversely, activation of D1 receptors facilitated the maintenance of LTP, and this effect is impaired in heterozygous D1 receptor knockout mice. Low-frequency stimulation induced a transient depression in the medial prefrontal cortex. This depression could be transformed into LTD by coapplication of dopamine. Coapplication of dopamine, however, shows no facilitating effect on LTD in heterozygous D1 receptor knockout mice. These results provide pharmacological and genetic evidence for a role of D1 receptors in the bidirectional modulation of synaptic plasticity in the medial prefrontal cortex. The absence of this modulation in heterozygous knockout mice shows that a dysregulation of dopamine receptor expression levels can have dramatic effects on synaptic plasticity in the prefrontal cortex.