Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Brain Res. 2013 May 20;1511:73-92. doi: 10.1016/j.brainres.2012.11.001. Epub 2012 Nov 8.
The neural circuits underlying emotional valence and motivated behaviors are several synapses away from both defined sensory inputs and quantifiable motor outputs. Electrophysiology has provided us with a suitable means for observing neural activity during behavior, but methods for controlling activity for the purpose of studying motivated behaviors have been inadequate: electrical stimulation lacks cellular specificity and pharmacological manipulation lacks temporal resolution. The recent emergence of optogenetic tools provides a new means for establishing causal relationships between neural activity and behavior. Optogenetics, the use of genetically-encodable light-activated proteins, permits the modulation of specific neural circuit elements with millisecond precision. The ability to control individual cell types, and even projections between distal regions, allows us to investigate functional connectivity in a causal manner. The greatest consequence of controlling neural activity with finer precision has been the characterization of individual neural circuits within anatomical brain regions as defined functional units. Within the mesolimbic dopamine system, optogenetics has helped separate subsets of dopamine neurons with distinct functions for reward, aversion and salience processing, elucidated GABA neuronal effects on behavior, and characterized connectivity with forebrain and cortical structures. Within the striatum, optogenetics has confirmed the opposing relationship between direct and indirect pathway medium spiny neurons (MSNs), in addition to characterizing the inhibition of MSNs by cholinergic interneurons. Within the hypothalamus, optogenetics has helped overcome the heterogeneity in neuronal cell-type and revealed distinct circuits mediating aggression and feeding. Within the amygdala, optogenetics has allowed the study of intra-amygdala microcircuitry as well as interconnections with distal regions involved in fear and anxiety. In this review, we will present the body of optogenetic studies that has significantly enhanced our understanding of emotional valence and motivated behaviors. This article is part of a Special Issue entitled Optogenetics (7th BRES).
神经回路是情绪效价和动机行为的基础,它们与明确的感觉输入和可量化的运动输出相隔几个突触。电生理学为我们提供了一种在行为过程中观察神经活动的合适手段,但用于研究动机行为的活动控制方法还不够完善:电刺激缺乏细胞特异性,药物操纵缺乏时间分辨率。最近出现的光遗传学工具为在神经活动和行为之间建立因果关系提供了一种新的手段。光遗传学是指使用遗传可编码的光激活蛋白,它可以以毫秒级的精度调节特定的神经回路元件。控制单个细胞类型甚至远距离投射的能力使我们能够以因果关系的方式研究功能连接。控制神经活动的精度提高带来的最大结果是将解剖大脑区域内的单个神经回路描述为特定的功能单元。在中脑边缘多巴胺系统中,光遗传学有助于将具有不同奖赏、厌恶和突显处理功能的多巴胺神经元亚群分开,阐明 GABA 神经元对行为的影响,并描述与前脑和皮质结构的连接。在纹状体中,光遗传学证实了直接和间接通路中间神经元(MSN)之间的对立关系,此外还描述了胆碱能中间神经元对 MSN 的抑制作用。在下丘脑中,光遗传学有助于克服神经元细胞类型的异质性,并揭示了介导攻击和进食的不同回路。在杏仁核中,光遗传学允许研究内杏仁核微电路以及与恐惧和焦虑相关的远距离区域的连接。在这篇综述中,我们将介绍大大增强了我们对情绪效价和动机行为的理解的光遗传学研究。本文是题为“光遗传学(第 7 期 BRES)”的特刊的一部分。