Luther Jason A, Birren Susan J
Department of Biology, National Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.
Auton Neurosci. 2009 Nov 17;151(1):46-60. doi: 10.1016/j.autneu.2009.08.009. Epub 2009 Sep 13.
The electrical and synaptic properties of neurons are essential for determining the function of the nervous system. Thus, understanding the mechanisms that control the appropriate developmental acquisition and maintenance of these properties is a critical problem in neuroscience. A great deal of our understanding of these developmental mechanisms comes from studies of soluble growth factor signaling between cells in the peripheral nervous system. The sympathetic nervous system has provided a model for studying the role of these factors both in early development and in the establishment of mature properties. In particular, neurotrophins produced by the targets of sympathetic innervation regulate the synaptic and electrophysiological properties of postnatal sympathetic neurons. In this review we examine the role of neurotrophin signaling in the regulation of synaptic strength, neurotransmitter phenotype, voltage-gated currents and repetitive firing properties of sympathetic neurons. Together, these properties determine the level of sympathetic drive to target organs such as the heart. Changes in this sympathetic drive, which may be linked to dysfunctions in neurotrophin signaling, are associated with devastating diseases such as high blood pressure, arrhythmias and heart attack. Neurotrophins appear to play similar roles in modulating the synaptic and electrical properties of other peripheral and central neuronal systems, suggesting that information provided from studies in the sympathetic nervous system will be widely applicable for understanding the neurotrophic regulation of neuronal function in other systems.
神经元的电学和突触特性对于确定神经系统的功能至关重要。因此,了解控制这些特性在发育过程中适当获得和维持的机制是神经科学中的一个关键问题。我们对这些发育机制的大量了解来自于对周围神经系统中细胞间可溶性生长因子信号传导的研究。交感神经系统为研究这些因子在早期发育和成熟特性建立中的作用提供了一个模型。特别是,由交感神经支配的靶标产生的神经营养因子调节出生后交感神经元的突触和电生理特性。在这篇综述中,我们研究了神经营养因子信号传导在调节交感神经元的突触强度、神经递质表型、电压门控电流和重复放电特性中的作用。这些特性共同决定了对诸如心脏等靶器官的交感驱动水平。这种交感驱动的变化可能与神经营养因子信号传导功能障碍有关,与高血压、心律失常和心脏病发作等毁灭性疾病相关。神经营养因子在调节其他周围和中枢神经元系统的突触和电学特性方面似乎也发挥着类似作用,这表明来自交感神经系统研究的信息将广泛适用于理解其他系统中神经元功能的神经营养调节。