Ih channels contribute to the different functional properties of identified dopaminergic subpopulations in the midbrain
Ih channels contribute to the different functional properties of identified dopaminergic subpopulations in the midbrain
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DOI：
10.1523/jneurosci.22-04-01290.2002
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发表时间：
2002-02-15
影响因子：
5.3
通讯作者：
Roeper, J
中科院分区：
文献类型：
--
作者：
Neuhoff, H;Neu, A;Roeper, J
黑质（SN）和腹侧被盖区（VTA）中的多巴胺能（DA）中脑神经元参与各种脑功能，如自主运动和奖励，并且是帕金森病和精神分裂症等疾病的靶点。为了研究小鼠中脑切片中识别出的DA神经元的功能特性，我们将膜片钳记录与神经生物素细胞填充和三重标记共聚焦免疫组化或单细胞RT-PCR相结合。我们根据解剖学和神经化学差异区分了四个DA亚群：两个在黑质（SN/CB+）或腹侧被盖区（VTA/CB+）表达钙结合蛋白D-28-k（CB）的DA群体，以及两个钙结合蛋白D-28-k阴性DA群体（SN/CB-，VTA/CB-）。与其他DA神经元相比，VTA/ CB+ DA神经元显示出更快的起搏频率和更小的后超极化。与此相反，所有四个DA群体具有显着差异的I-h通道密度和I-h通道介导的功能特性，如下垂幅度和反弹延迟，按照以下顺序：SN/CB-> VTA/ CB-> SN/CB+ --> VTA/CB+。单细胞RT-多重PCR实验表明，差异钙结合蛋白，但不是钙视网膜蛋白的表达与差异Ih通道密度。然而，只有在SN/CB-DA神经元中，I-h通道积极参与起搏频率控制。总之，DA系统内的多样性不仅限于不同的轴突投射和突触连接的差异，而且还涉及神经化学和地形不同的DA神经元之间的突触后电导的差异。
Dopaminergic (DA) midbrain neurons in the substantia nigra (SN) and ventral tegmental area (VTA) are involved in various brain functions such as voluntary movement and reward and are targets in disorders such as Parkinson's disease and schizophrenia. To study the functional properties of identified DA neurons in mouse midbrain slices, we combined patch-clamp recordings with either neurobiotin cell-filling and triple labeling confocal immunohistochemistry, or single-cell RT-PCR. We discriminated four DA subpopulations based on anatomical and neurochemical differences: two calbindin D-28-k (CB) expressing DA populations in the substantia nigra (SN/CB+) or ventral tegmental area (VTA/CB+), and respectively, two calbindin D-28-k negative DA populations (SN/CB-, VTA/CB-). VTA/ CB+ DA neurons displayed significantly faster pacemaker frequencies with smaller afterhyperpolarizations compared with other DA neurons. In contrast, all four DA populations possessed significant differences in I-h channel densities and I-h channel-mediated functional properties like sag amplitudes and rebound delays in the following order: SN/CB- --> VTA/ CB- --> SN/CB+ --> VTA/CB+. Single-cell RT-multiplex PCR experiments demonstrated that differential calbindin but not calretinin expression is associated with differential Ih channel densities. Only in SN/CB- DA neurons, however, I-h channels were actively involved in pacemaker frequency control. In conclusion, diversity within the DA system is not restricted to distinct axonal projections and differences in synaptic connectivity, but also involves differences in postsynaptic conductances between neurochemically and topographically distinct DA neurons.