Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, MA 02478, USA.
Pharmacol Biochem Behav. 2018 Nov;174:64-79. doi: 10.1016/j.pbb.2017.05.005. Epub 2017 May 11.
Understanding complex behavioral processes, both learned and innate, requires detailed characterization of the principles governing signal flow in corresponding neural circuits. Previous studies were hampered by the lack of appropriate tools needed to address the complexities of behavior-driving micro- and macrocircuits. The development and implementation of optogenetic methodologies revolutionized the field of behavioral neuroscience, allowing precise spatiotemporal control of specific, genetically defined neuronal populations and their functional connectivity both in vivo and ex vivo, thus providing unprecedented insights into the cellular and network-level mechanisms contributing to behavior. Here, we review recent pioneering advances in behavioral studies with optogenetic tools, focusing on mechanisms of fear-related behavioral processes with an emphasis on approaches which could be used to suppress fear when it is pathologically expressed. We also discuss limitations of these methodologies as well as review new technological developments which could be used in future mechanistic studies of fear behavior.
理解复杂的行为过程,包括习得和先天的,需要详细描述控制相应神经回路中信号流的原则。以前的研究受到缺乏适当工具的阻碍,这些工具是解决行为驱动的微观和宏观电路复杂性所必需的。光遗传学方法的发展和实施彻底改变了行为神经科学领域,允许在体内和体外精确地控制特定的、遗传定义的神经元群体及其功能连接,从而为行为的细胞和网络水平机制提供了前所未有的见解。在这里,我们回顾了使用光遗传学工具进行行为研究的最新开创性进展,重点介绍了与恐惧相关的行为过程的机制,强调了在病理性表达恐惧时可以用来抑制恐惧的方法。我们还讨论了这些方法的局限性,并回顾了未来恐惧行为的机制研究中可能使用的新技术发展。