Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147; email:
Annu Rev Neurosci. 2014;37:387-407. doi: 10.1146/annurev-neuro-071013-014048. Epub 2014 Jun 16.
Elucidating the roles of neuronal cell types for physiology and behavior is essential for understanding brain functions. Perturbation of neuron electrical activity can be used to probe the causal relationship between neuronal cell types and behavior. New genetically encoded neuron perturbation tools have been developed for remotely controlling neuron function using small molecules that activate engineered receptors that can be targeted to cell types using genetic methods. Here we describe recent progress for approaches using genetically engineered receptors that selectively interact with small molecules. Called "chemogenetics," receptors with diverse cellular functions have been developed that facilitate the selective pharmacological control over a diverse range of cell-signaling processes, including electrical activity, for molecularly defined cell types. These tools have revealed remarkably specific behavioral physiological influences for molecularly defined cell types that are often intermingled with populations having different or even opposite functions.
阐明神经元细胞类型在生理和行为中的作用对于理解大脑功能至关重要。干扰神经元的电活动可以用来探究神经元细胞类型与行为之间的因果关系。已经开发出了新的遗传编码神经元干扰工具，这些工具可以使用小分子远程控制神经元的功能，这些小分子可以通过遗传方法靶向特定的细胞类型，激活工程受体。在这里，我们描述了使用遗传工程受体的最新进展，这些受体可以选择性地与小分子相互作用，称为“化学遗传学”。已经开发出了具有多种细胞功能的受体，这些受体促进了对多种细胞信号转导过程的选择性药理学控制，包括电活动，针对的是分子定义的细胞类型。这些工具揭示了对于分子定义的细胞类型的显著特异性的生理影响，这些影响通常与具有不同甚至相反功能的细胞群体交织在一起。
