An intrinsic neuronal oscillator underlies dopaminergic neuron bursting.
An intrinsic neuronal oscillator underlies dopaminergic neuron bursting.
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DOI：
10.1523/jneurosci.4053-09.2009
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发表时间：
2009-12-16
期刊：
影响因子：
--
通讯作者：
Paladini CA
中科院分区：
文献类型：
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作者：
Deister CA;Teagarden MA;Wilson CJ;Paladini CA
当动物受到意外的奖励或预测奖励的刺激时，中脑腹侧的多巴胺能神经元会发出高频脉冲。为了确定可以启动爆发的传入神经，并为受改变的爆发影响的疾病建立治疗策略，对爆发的机械理解是必不可少的。我们的研究结果表明，爆发是由NMDA受体和电压门控离子通道的电压敏感性之间的特定相互作用，这导致激活的内在的，动作电位独立的，高频膜电位振荡。我们进一步表明，NMDA受体是唯一适合于这一点，因为快速的动力学和电压依赖性赋予它的Mg 2+离子阻断和解除阻断。这种机制解释了多巴胺能细胞爆发的离散性，并证明了突触信号如何在影响动作电位产生之前被神经元的局部内在特性重塑。
Dopaminergic neurons of the ventral midbrain fire high frequency bursts when animals are presented with unexpected rewards, or stimuli that predict reward. To identify the afferents that can initiate bursting and establish therapeutic strategies for diseases affected by altered bursting, a mechanistic understanding of bursting is essential. Our results show that bursting is initiated by a specific interaction between the voltage sensitivity of NMDA receptors and voltage-gated ion channels, which result in the activation of an intrinsic, action potential-independent, high-frequency membrane potential oscillation. We further show that the NMDA receptor is uniquely suited for this because of the rapid kinetics and voltage dependence imparted to it by Mg2+ ion block and unblock. This mechanism explains the discrete nature of bursting in dopaminergic cells, and demonstrates how synaptic signals may be reshaped by local intrinsic properties of a neuron before influencing action potential generation.