Why I Am Not SHY: A Reply to Tononi and Cirelli

In a recent article I reviewed an influential theory of sleep function, the “synaptic homeostasis hypothesis (SHY.)” According to SHY, sleep renormalizes synapses that are potentiated during prior wakefulness. I concluded that while SHY is a seminal theory with important implications about sleep function and the brain, its underlying mechanisms are poorly defined. In an accompanying article, the authors of SHY responded at length. Their reply is thoughtful and provocative, but unfortunately many of the points I raised were not accurately represented or addressed. In this brief commentary, I attempt to clarify some points of confusion. I also explain why any theory of sleep function is incomplete without an understanding of the underlying cellular mechanisms. 1. Introduction In their companion article, Tononi and Cirelli argue that I have missed the big picture by conflating questions of sleep function with the underlying mechanisms [1]. As I have discussed elsewhere [2, 3], understanding sleep function is of central importance to biology. Any theory of sleep function must also grapple with universal traits of sleep, some of which were enumerated in their response. There are other theories of sleep function and many of the theoretical arguments made in support of SHY (e.g., a need for offline states, sleep homeostasis, and brain metabolism) apply to them. These are not the issues at hand. The issue is how should scientists evaluate these theories? My position is that this evaluation must always include a discussion of mechanisms, because they cannot be disentangled from functional questions. The underlying message from Tononi and Cirelli is that what really matters is the “…the end result” [1, page 4] rather than how you get there. I find this an odd position to take and a backward step in our pursuit of sleep function. The goal of science is to understand how nature works. That includes an empirical pursuit of physical mechanisms. This in part distinguishes science from pure philosophy. Scientists should therefore be skeptical of any theory of sleep function that fails to elucidate the underlying mechanisms that govern the proposed function. In this regard, the proponents of SHY are in an indefensible position when they argue that the mechanisms have “…no bearing on whether the core claim of SHY is true or false” [1, page 3]. They have bearing because if the underlying mechanisms are not sleep dependent then the theory is wrong. Incidentally, the theory is also wrong if the proposed mechanisms do not exist. While it may be true that these mechanisms are