Purinergic Modulation of Neuronal Activity in Developing Auditory Brainstem
Purinergic Modulation of Neuronal Activity in Developing Auditory Brainstem
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DOI：
10.1523/jneurosci.0372-12.2012
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发表时间：
2012-08-01
影响因子：
5.3
通讯作者：
Milenkovic, Ivan
中科院分区：
文献类型：
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作者：
Dietz, Beatrice;Jovanovic, Sasa;Milenkovic, Ivan
在发育中的神经系统中，自发的神经元活动独立于经验或任何环境输入而产生。这种活动可能在轴突寻路、地形图细化、树突形态发生和轴突末端乔木的分离中发挥重要作用。在听觉系统中，耳蜗中内源释放的 ATP 会激活内毛细胞，触发动作电位 (AP) 爆发，然后将其传输到中枢听觉系统。在这里，我们展示了耳蜗以外的嘌呤能信号的调节作用，即对蒙古沙鼠听觉脑干神经元的发育调节和细胞类型特异性去极化作用。我们评估了从预听到听觉信号处理早期阶段 P2X 受体 (P2XR) 对神经元兴奋性的影响。我们的结果表明，在表达 P2XR 的神经元中，细胞外 ATP 可以与 Ca2+ 信号同步唤起 AP。在耳蜗核 (CN) 浓密细胞中，ATP 会增加体内自发活动和声诱发活动，但这些作用会随着成熟而减弱。此外，ATP 不仅增强了谷氨酸驱动的放电，而且在没有谷氨酸传递的情况下也诱发了 AP。体内记录还表明，CN 中内源释放的 ATP 通过促进 AP 生成和延长 AP 持续时间来促进神经元放电活动。鉴于 ATP 对 AP 放电的增强作用以及 P2XR 对某些听觉脑干核以及这些核内不同神经元的限制，可以想象嘌呤能信号在神经元脑干回路的发育中发挥特定作用。
In the developing nervous system, spontaneous neuronal activity arises independently of experience or any environmental input. This activity may play a major role in axonal pathfinding, refinement of topographic maps, dendritic morphogenesis, and the segregation of axonal terminal arbors. In the auditory system, endogenously released ATP in the cochlea activates inner hair cells to trigger bursts of action potentials (APs), which are transferred to the central auditory system. Here we show the modulatory role of purinergic signaling beyond the cochlea, i.e., the developmentally regulated and cell-type-specific depolarizing effects on auditory brainstem neurons of Mongolian gerbil. We assessed the effects of P2X receptors (P2XRs) on neuronal excitability from prehearing to early stages of auditory signal processing. Our results demonstrate that in neurons expressing P2XRs, extracellular ATP can evoke APs in sync with Ca2+ signals. In cochlear nucleus (CN) bushy cells, ATP increases spontaneous and also acoustically evoked activity in vivo, but these effects diminish with maturity. Moreover, ATP not only augmented glutamate-driven firing, but it also evoked APs in the absence of glutamatergic transmission. In vivo recordings also revealed that endogenously released ATP in the CN contributes to neuronal firing activity by facilitating AP generation and prolonging AP duration. Given the enhancing effect of ATP on AP firing and confinement of P2XRs to certain auditory brainstem nuclei, and to distinct neurons within these nuclei, it is conceivable that purinergic signaling plays a specific role in the development of neuronal brainstem circuits.