Kash Thomas L, Pleil Kristen E, Marcinkiewcz Catherine A, Lowery-Gionta Emily G, Crowley Nicole, Mazzone Christopher, Sugam Jonathan, Hardaway J Andrew, McElligott Zoe A
Bowles Center for Alcohol Studies and Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, USA.
Mol Cells. 2015 Jan 31;38(1):1-13. doi: 10.14348/molcells.2015.2261. Epub 2014 Dec 4.
Recent technical developments have transformed how neuroscientists can probe brain function. What was once thought to be difficult and perhaps impossible, stimulating a single set of long range inputs among many, is now relatively straight-forward using optogenetic approaches. This has provided an avalanche of data demonstrating causal roles for circuits in a variety of behaviors. However, despite the critical role that neuropeptide signaling plays in the regulation of behavior and physiology of the brain, there have been remarkably few studies demonstrating how peptide release is causally linked to behaviors. This is likely due to both the different time scale by which peptides act on and the modulatory nature of their actions. For example, while glutamate release can effectively transmit information between synapses in milliseconds, peptide release is potentially slower [See the excellent review by Van Den Pol on the time scales and mechanisms of release (van den Pol, 2012)] and it can only tune the existing signals via modulation. And while there have been some studies exploring mechanisms of release, it is still not as clearly known what is required for efficient peptide release. Furthermore, this analysis could be complicated by the fact that there are multiple peptides released, some of which may act in contrast. Despite these limitations, there are a number of groups making progress in this area. The goal of this review is to explore the role of peptide signaling in one specific structure, the bed nucleus of the stria terminalis, that has proven to be a fertile ground for peptide action.
最近的技术发展改变了神经科学家探究大脑功能的方式。曾经被认为困难甚至可能无法做到的事情,即在众多长程输入中刺激单一的一组长程输入,现在使用光遗传学方法相对简单。这提供了大量数据,证明了神经回路在各种行为中的因果作用。然而,尽管神经肽信号在大脑行为和生理调节中起着关键作用,但很少有研究证明肽释放与行为之间的因果联系。这可能是由于肽发挥作用的时间尺度不同以及其作用的调节性质。例如,虽然谷氨酸释放可以在几毫秒内有效地在突触之间传递信息,但肽释放可能较慢[见范登·波尔关于释放时间尺度和机制的精彩综述(范登·波尔,2012年)],并且它只能通过调节来调整现有的信号。虽然已经有一些研究探索释放机制,但高效肽释放所需的条件仍不太清楚。此外,由于释放多种肽,其中一些可能起相反作用,这一分析可能会变得复杂。尽管存在这些限制,但仍有许多研究小组在这一领域取得进展。本综述的目的是探讨肽信号在一个特定结构——终纹床核中的作用,该结构已被证明是肽发挥作用的沃土。