The hypocretin story

Abstract

The main topic of this book stems from the discovery of two neuropeptides derived from the same precursor, conducted in parallel by two different groups (de Lecea et al. in Proc Natl Acad Sci USA 95:322-327, 1998; Sakurai et al. in Cell 92:573-585, 1998). Here is the account of the discovery of the hypocretin peptides, which was the result of a larger effort to characterize patterns of gene expression in the brain. The original hypothesis leading to the discovery of the peptides was that new mechanisms underlying the many functions of the hypothalamus (e.g. feeding, thermoregulation, circadian rhythmicity, sexual behavior and arousal) could be unraveled by identifying the expression patterns of hundreds of "cell-type" specific transcripts. This hypothesis ended up converging with a reverse pharmacology approach followed by Yanagisawa and colleagues, which is described in detail in other chapters. With the hypocretin story in the background, I also describe here the first implementation of optogenetic methods in a freely moving animal, which has led to a revolution in systems neuroscience.