Laboratory of Molecular Genetics, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Cell. 2012 Nov 21;151(5):1126-37. doi: 10.1016/j.cell.2012.10.039.
The mammalian brain is composed of thousands of interacting neural cell types. Systematic approaches to establish the molecular identity of functional populations of neurons would advance our understanding of neural mechanisms controlling behavior. Here, we show that ribosomal protein S6, a structural component of the ribosome, becomes phosphorylated in neurons activated by a wide range of stimuli. We show that these phosphorylated ribosomes can be captured from mouse brain homogenates, thereby enriching directly for the mRNAs expressed in discrete subpopulations of activated cells. We use this approach to identify neurons in the hypothalamus regulated by changes in salt balance or food availability. We show that galanin neurons are activated by fasting and that prodynorphin neurons restrain food intake during scheduled feeding. These studies identify elements of the neural circuit that controls food intake and illustrate how the activity-dependent capture of cell-type-specific transcripts can elucidate the functional organization of a complex tissue.
哺乳动物的大脑由数千种相互作用的神经细胞类型组成。系统的方法来确定神经元功能群体的分子特征将有助于我们理解控制行为的神经机制。在这里，我们表明核糖体蛋白 S6（核糖体的结构成分）在受广泛刺激激活的神经元中发生磷酸化。我们表明，这些磷酸化核糖体可以从小鼠脑匀浆中捕获，从而直接富集在激活细胞的离散亚群中表达的 mRNA。我们使用这种方法来鉴定受盐平衡或食物供应变化调节的下丘脑神经元。我们表明，禁食会激活甘丙肽神经元，而前原啡肽神经元在定时喂养期间抑制摄食。这些研究确定了控制摄食的神经回路的组成部分，并说明了如何通过活性依赖性捕获细胞类型特异性转录本来阐明复杂组织的功能组织。
