Science2014-06-10 5:10 PM

增加大脑钾离子通道的电流会让抑郁消失 Enhancing Depression Mechanisms in Midbrain Dopamine Neurons Achieves Homeostatic Resilience


过去的研究显示,当小鼠体内阳离子通道的电流增加时,其脑中腹侧被盖区 (VTA) 中的多巴胺神经元会变得过度活跃,并转而使这些小鼠变得抑郁。然而,Allyson Friedman及其同事现在发现,增加这些离子通道的电流甚至会进一步导致一种令人惊讶的效应:它会完全消除小鼠的抑郁症。





Typical therapies try to reverse pathogenic mechanisms. Here, we describe treatment effects achieved by enhancing depression-causing mechanisms in ventral tegmental area (VTA) dopamine (DA) neurons. In a social defeat stress model of depression, depressed (susceptible) mice display hyperactivity of VTA DA neurons, caused by an up-regulated hyperpolarization-activated current (Ih). Mice resilient to social defeat stress, however, exhibit stable normal firing of these neurons. Unexpectedly, resilient mice had an even larger Ih, which was observed in parallel with increased potassium (K+) channel currents. Experimentally further enhancing Ih or optoGENEtically increasing the hyperactivity of VTA DA neurons in susceptible mICE completely reversed depression-related behaviors, an antidepressant effect achieved through resilience-like, projection-specific homeostatic plasticity. These results indicate a potential therapeutic path of promoting natural resilience for depression treatment.

Editor's Summary

Resilient Hyperpolarization

Despite constant exposure to all sorts of stressors, most people are resilient and do not develop depression, but we do not understand the neurophysiological underpinnings of stress resilience. Friedman et al. (p. 313) studied this phenomenon in a mouse model of social-defeat stress depression. In the mice they found that, despite apparently pathological levels of hyperpolarization and elevated potassium channel currents in the ventral tegmental area (a structure known to be involved in depression), resilient mice showed normal activity in dopaminergic neurons. Thus, if “depressed” mice were experimentally provoked into hyperpolarization—unexpectedly, they completely reversed depression-related behaviors.






Science Magazine

0 Following 18 Fans 0 Projects 236 Articles


AbstractThe conservation of sleep across all animal species suggests that sleep serves a vital function. We here report that sleep has a critical funct

Read More

Introduction Recent decades have seen a major international effort to inventory tree communities in the Amazon Basin and Guiana Shield (Amazonia), but

Read More

IntroductionInitiation of protein synthesis is a key step in the control of gene expression. In eukaryotes, initiation is a highly complex process that

Read More

Abstract For decades, social psychological theories have posited that the automatic processes captured by implicit measures have implications for soci

Read More


Read More

论文摘要 首先,在一篇“评论”文章中,Thomas Piketty 和 Emmanuel Saez用“世界顶级收入数据库(WTID)”来比较这两个数值多年来是如何在欧洲和美国演变的;WTID包括了一个世纪之久的有关全球收入的数据以及2个世纪之久的有关个人财富的数据。据研究人员披露,在20世纪之交的时候

Read More

IntroductionCensorship has a long history in China, extending from the efforts of Emperor Qin to burn Confucian texts in the third century BCE to the c

Read More

Many animals, on air, water, or land, navigate in three-dimensional (3D) environments, yet it remains unclear how brain circuits encode the animal's 3D

Read More

Many animals, on air, water, or land, navigate in three-dimensional (3D) environments, yet it remains unclear how brain circuits encode the animal's 3D

Read More

Like mammalian neurons, Caenorhabditis elegans neurons lose axon regeneration ability as they age, but it is not known why. Here, we report that let-7

Read More