Emotions, cognition, and consciousness emerge with the processing of neuronal information provided by memory readouts and senses. How this actually works seemed for a long time to be a question too big to ask. Advances in neuroscience have always been driven by methodological inventions, and current efforts to develop neurotechnologies are motivated by experimental strategies, including analytical dissection (that is, inverse engineering), large-scale interrogation, and synthetic reconstruction of the mammalian cerebral cortex (which is important for higher cognitive functions) and connected brain structures (1, 2). As part of this neurotechnological endeavor, mapping the transcriptome of neurons with single-cell resolution and with known three-dimensional tissue localization has been a long-sought enabling technology (3). On page 380 of this issue, Wang et al. (4) present the technology and workflow to access transcriptional states of more than 100 genes from up to 30,000 cells in a cubic millimeter of cortical tissue. This advanced methodology will facilitate studies that improve our understanding of the neuronal hardware and, when combined with other emerging neurotechnologies, will enable big questions in neuroscience to be addressed.