Wang Sheng, Polo-Parada Luis, Landmesser Lynn T
Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4975, USA.
J Neurosci. 2009 Dec 2;29(48):15232-44. doi: 10.1523/JNEUROSCI.3809-09.2009.
In the nervous system, spontaneous Ca(2+) transients play important roles in many developmental processes. We previously found that altering the frequency of electrically recorded rhythmic spontaneous bursting episodes in embryonic chick spinal cords differentially perturbed the two main pathfinding decisions made by motoneurons, dorsal-ventral and pool-specific, depending on the sign of the frequency alteration. Here, we characterized the Ca(2+) transients associated with these bursts and showed that at early stages while motoneurons are still migrating and extending axons to the base of the limb bud, they display spontaneous, highly rhythmic, and synchronized Ca(2+) transients. Some precursor cells in the ependymal layer displayed similar transients. T-type Ca(2+) channels and a persistent Na(+) current were essential to initiate spontaneous bursts and associated transients. However, subsequent propagation of activity throughout the cord resulted from network-driven chemical transmission mediated presynaptically by Ca(2+) entry through N-type Ca(2+) channels and postsynaptically by acetylcholine acting on nicotinic receptors. The increased Ca(2+) during transients depended primarily on L-type and T-type channels with a modest contribution from TRP (transient receptor potential) channels and ryanodine-sensitive internal stores. Significantly, the drugs used previously to produce pathfinding errors altered transient frequency but not duration or amplitude. These observations imply that different transient frequencies may differentially modulate motoneuron pathfinding. However, the duration of the Ca(2+) transients differed significantly between pools, potentially enabling additional distinct pool-specific downstream signaling. Many early events in spinal motor circuit formation are thus potentially sensitive to the rhythmic Ca(2+) transients we have characterized and to any drugs that perturb them.
在神经系统中，自发性Ca(2+)瞬变在许多发育过程中发挥着重要作用。我们之前发现，改变胚胎期鸡脊髓中电记录的节律性自发爆发事件的频率，会根据频率改变的正负，以不同方式干扰运动神经元做出的两个主要路径寻找决定，即背腹向和池特异性决定。在此，我们对与这些爆发相关的Ca(2+)瞬变进行了特征描述，并表明在早期阶段，当运动神经元仍在迁移并将轴突延伸至肢芽基部时，它们会表现出自发性、高度节律性且同步的Ca(2+)瞬变。室管膜层中的一些前体细胞也表现出类似的瞬变。T型Ca(2+)通道和持续性Na(+)电流对于启动自发爆发及相关瞬变至关重要。然而，随后活动在整个脊髓中的传播是由网络驱动的化学传递介导的，突触前通过Ca(2+)经N型Ca(2+)通道内流，突触后通过乙酰胆碱作用于烟碱型受体。瞬变期间[Ca(2+)]i的增加主要依赖于L型和T型通道，TRP（瞬时受体电位）通道和兰尼碱敏感的内部储存也有一定贡献。重要的是，先前用于产生路径寻找错误的药物改变了瞬变频率，但未改变其持续时间或幅度。这些观察结果表明，不同的瞬变频率可能以不同方式调节运动神经元的路径寻找。然而，不同运动神经元池之间Ca(2+)瞬变的持续时间存在显著差异，这可能使下游产生额外的、不同的池特异性信号。因此，脊髓运动回路形成过程中的许多早期事件可能对我们所描述的节律性Ca(2+)瞬变以及任何干扰它们的药物敏感。
