Cellular mechanisms underlying burst firing in substantia nigra dopamine neurons.
Cellular mechanisms underlying burst firing in substantia nigra dopamine neurons.
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DOI：
10.1523/jneurosci.2961-09.2009
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发表时间：
2009-12-09
期刊：
影响因子：
--
通讯作者：
Bevan MD
中科院分区：
文献类型：
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作者：
Blythe SN;Wokosin D;Atherton JF;Bevan MD
黑质多巴胺（SN DA）神经元的爆发性放电被认为是指导突触可塑性和联想学习的重要教学信号。然而，突触兴奋克服体细胞Ca ~（2+）依赖性K ~+电流的限制作用产生爆发性放电的机制仍有争议。建模研究表明，突触兴奋充分放大振荡树突状Ca 2+和Na+通道电流，导致在SN DA神经元树突的高频发射的启动。为了测试该模型，在体外将视觉引导的隔室特异性膜片钳记录和离子通道操纵应用于啮齿动物SN DA神经元。如前所述，SN DA神经元的轴突通常被发现起源于接近索马的大直径树突。然而，与模型的预测相反：1）体细胞电流注入产生的放电在频率和形式上与体内爆发放电相似; 2）突触能兴奋的功效与兴奋与轴突的距离成负相关; 3）药理学阻断或遗传删除Ca 2+通道并不能阻止高频放电; 4）动作电位爆发总是首先在轴突近端检测到; 5）轴突/索马附近的Na+通道的药理学阻断而不是树突兴奋损害爆发放电。总之，这些数据表明，SN DA神经元整合他们的突触输入在一个更传统的方式比以前假设的。
Burst firing of substantia nigra dopamine (SN DA) neurons is believed to represent an important teaching signal that instructs synaptic plasticity and associative learning. However, the mechanisms through which synaptic excitation overcomes the limiting effects of somatic Ca2+-dependent K+ current to generate burst firing are controversial. Modeling studies suggest that synaptic excitation sufficiently amplifies oscillatory dendritic Ca2+ and Na+ channel currents to lead to the initiation of high-frequency firing in SN DA neuron dendrites. In order to test this model visually guided compartment-specific patch clamp recording and ion channel manipulation were applied to rodent SN DA neurons in vitro. As previously suggested, the axon of SN DA neurons was typically found to originate from a large diameter dendrite that was proximal to the soma. However, in contrast to the predictions of the model: 1) somatic current injection generated firing that was similar in frequency and form to burst firing in vivo; 2) the efficacy of glutamatergic excitation was inversely related to the distance of excitation from the axon; 3) pharmacological blockade or genetic deletion of Ca2+ channels did not prevent high-frequency firing; 4) action potential bursts were invariably detected first at sites that were proximal to the axon; 5) pharmacological blockade of Na+ channels in the vicinity of the axon/soma but not dendritic excitation impaired burst firing. Together, these data suggest that SN DA neurons integrate their synaptic input in a more conventional manner than was previously hypothesized.