Department of Physiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
J Neurosci. 2009 Dec 9;29(49):15531-41. doi: 10.1523/JNEUROSCI.2961-09.2009.
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 Ca(2+)-dependent K(+) current to generate burst firing are controversial. Modeling studies suggest that synaptic excitation sufficiently amplifies oscillatory dendritic Ca(2+) and Na(+) channel currents to lead to the initiation of high-frequency firing in SN DA neuron dendrites. 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 suggested previously, 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 Ca(2+) channels did not prevent high-frequency firing, (4) action potential bursts were invariably detected first at sites that were proximal to the axon, and (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 hypothesized previously.
黑质多巴胺（SN DA）神经元的爆发式放电被认为是一种重要的教学信号，它指导着突触可塑性和联想学习。然而，突触兴奋克服体细胞钙离子依赖性钾电流的限制作用以产生爆发式放电的机制仍存在争议。建模研究表明，突触兴奋足以放大振荡树突钙离子和钠离子通道电流，从而导致 SN DA 神经元树突中高频放电的起始。为了验证该模型，对体外啮齿类动物 SN DA 神经元进行了视觉引导的特定部位膜片钳记录和离子通道操作。如前所述，SN DA 神经元的轴突通常起源于靠近体细胞的大直径树突。然而，与模型的预测相反，（1）体细胞电流注入产生的放电频率和形式与体内的爆发式放电相似，（2）谷氨酸能兴奋的功效与兴奋与轴突的距离成反比，（3）钙通道的药理学阻断或基因缺失并不能阻止高频放电，（4）动作电位爆发总是首先在靠近轴突的部位检测到，（5）轴突/体细胞附近的钠离子通道药理学阻断而不是树突兴奋损害了爆发式放电。总之，这些数据表明，SN DA 神经元以比以前假设的更传统的方式整合其突触输入。
