Homeostatic Plasticity and Maturation of Excitability During Embryonic Development of the Sympathetic Nervous System

项目总结： 交感神经系统(SNS)向周围靶器官提供直接的输出，影响 自主神经功能，如心率和血管收缩。社交网络的疾病通常与 过度兴奋性，如高血压。目前还不清楚这些疾病状态发生的原因。我们 可以预见，这可能部分归因于通过内环境平衡机制实现的兴奋性的变化。 可塑性。这种形式的可塑性可以包括突触后受体积累和离子通道的变化 电导，两者都作用于内稳态调节放电频率活动或突触效能的模式。 对电路中活动变化的反应。动态平衡机制在早期表达最旺盛 电路的发展。然而，我们预测，在兴奋性过程中诱导这些动态平衡变化 早期发育可能导致回路兴奋性的长期后果，潜在地离开 社交网络易受适应不良的过度兴奋的影响。这些机制以前从未在 社交网络。我们的实验室有丰富的经验证明鸡胚胎脊柱的动态平衡可塑性。 运动神经元，它来自一个祖细胞群体，也产生交感神经节前神经元 脊髓的神经元(SPN)。在脊髓自发网络发作时，SPN也是活跃的 活动，就像它们的运动神经元对应的。因此，我们希望看到动态平衡可塑性的证据。 在这些细胞中也是如此。此外，我们预计这些塑性机制可能存在于一个关键时期。 它存在于电路的早期发育过程中，与视觉系统的情况非常相似。中心假说 这项研究的主要内容是：1)SNS中的细胞将表现出平衡可塑性的机制；2)这种平衡可塑性 调节受关键期的支配，以及3)接受输入的交感神经节神经元(SGN) 从SPN直接投射到靶组织上，将显示出永久改变的交感音调或输出 在这种形式的可塑性的关键时期存在的早期动态平衡扰动之后。为了这些 鸡胚胎为胚胎发育提供了一个极好的模型，具有令人难以置信的可及性 观察和操纵，没有母性行为的混淆。这些结果是前所未有的 已经证实，并可能对长期健康和流行的人类疾病状态产生影响。

Project Summary: The sympathetic nervous system (SNS) provides direct output onto target organs in the periphery, effecting autonomic functions such as heart rate and vasoconstriction. Diseases of the SNS are often associated with hyperexcitability, such as in the case of hypertension. It is still unclear why these disease states occur. We predict that it may be due, in part, to changes in excitability that are achieved through mechanisms of homeostatic plasticity. This form of plasticity can include changes in postsynaptic receptor accumulation and ion channel conductance, which both work to homeostatically regulate patterns of firing rate activity or synaptic efficacy in response to alterations in activity in a circuit. Homeostatic mechanisms are most robustly expressed during early development of a circuit. However, we predict that inducing these homeostatic changes in excitability during early development may result in long term consequences in the excitability of the circuit, potentially leaving the SNS vulnerable to maladaptive hyperexcitability. These mechanisms have never before been demonstrated in the SNS. Our lab has ample experience demonstrating homeostatic plasticity in chick embryo spinal motoneurons, which arise from a progenitor cell population that also gives rise to sympathetic preganglionic neurons (SPNs) in the spinal cord. The SPNs are also active during bouts of spinal cord spontaneous network activity, just like their motoneuron counterparts. Therefore, we expect to see evidence of homeostatic plasticity in these cells as well. Furthermore, we expect that these plasticity mechanisms may exist during a critical period that exists during early development of the circuit, much like that of the visual system. The central hypotheses of this study are 1) that cells in the SNS will exhibit mechanisms of homeostatic plasticity, 2) that this homeostatic adjustment is governed by critical periods, and 3) that sympathetic ganglion neurons (SGNs), which receive input from the SPNs and project directly onto target tissue, will show a permanently altered sympathetic tone or output following an early homeostatic perturbation that exists in the critical period for this form of plasticity. For these aims, the chick embryo provides an excellent model for embryonic development with incredible accessibility for observation and manipulation, without the confounds of maternal behavior. These results have never before been demonstrated and may have implications for long-term health and prevalent human disease states.