Department of Pharmacology and Systems Therapeutics, Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY, USA.
Neuropharmacology. 2012 Jan;62(1):89-100. doi: 10.1016/j.neuropharm.2011.09.009. Epub 2011 Sep 17.
A continuously increasing body of knowledge shows that the brain is an extremely complex neural network and single neurons possess their own complicated interactive signaling pathways. Such complexity of the nervous system makes it increasingly difficult to investigate the functions of specific neural components such as genes, proteins, transcription factors, neurons and nuclei in the brain. Technically, it has been even more of a significant challenge to identify the molecular and cellular adaptations that are both sufficient and necessary to underlie behavioral functions in health and disease states. Defining such neural adaptations is a critical step to identify the potential therapeutic targets within the complex neural network that are beneficial to treat psychiatric disorders. Recently, the new development and extensive application of in vivo viral-mediated gene transfer (virogenetics) and optical manipulation of specific neurons or selective neural circuits in freely-moving animals (optogenetics) make it feasible, through loss- and gain-of-function approaches, to reliably define sufficient and necessary neuroadaptations in the behavioral models of psychiatric disorders, including drug addiction, depression, anxiety and bipolar disorders. In this article, we focus on recent studies that successfully employ these advanced virogenetic and optogenetic techniques as a powerful tool to identify potential targets in the brain, and to provide highly useful information in the development of novel therapeutic strategies for psychiatric disorders. This article is part of a Special Issue entitled 'Anxiety and Depression'.
越来越多的知识表明，大脑是一个极其复杂的神经网络，单个神经元拥有自己复杂的交互信号通路。神经系统的这种复杂性使得研究特定神经成分（如基因、蛋白质、转录因子、神经元和核）在健康和疾病状态下的功能变得越来越困难。从技术上讲，要确定分子和细胞的适应性，这既是充分的也是必要的，以作为健康和疾病状态下行为功能的基础，这是一个更大的挑战。定义这种神经适应性是确定复杂神经网络中潜在治疗靶点的关键步骤，这些靶点有利于治疗精神疾病。最近，体内病毒介导的基因转移（病毒遗传学）和在自由活动动物中对特定神经元或选择性神经回路进行光学操作（光遗传学）的新发展和广泛应用，使得通过失活和功能获得方法，在包括药物成瘾、抑郁、焦虑和双相情感障碍在内的精神疾病行为模型中可靠地定义充分和必要的神经适应性成为可能。本文重点介绍了最近的研究，这些研究成功地利用了这些先进的病毒遗传学和光遗传学技术，作为一种强大的工具来识别大脑中的潜在靶点，并为精神疾病的新型治疗策略的发展提供了非常有用的信息。本文是题为“焦虑和抑郁”的特刊的一部分。
