Lectures and seminars Nobel Laureate Revisiting Lecture – professor Michael W. Young

Behavioral and physiological regulators of sleep in Drosophila

Social isolation and loneliness have potent effects on public health. We used quantitative behavioral analysis and transcriptome profiling in Drosophila to explore brain states associated with persistent social isolation. Chronic social isolation alters the expression of metabolic genes and induces a brain state that resembles that of a starving fly. Accordingly, chronically isolated animals exhibit sleep loss accompanied by overconsumption of food. These responses to social isolation are driven by activities of a small group of neurons in the central brain of the fly. Artificial inactivation of these neurons suppresses these behavioral responses to chronic isolation, while their hyperactivation promotes sleep loss and excessive feeding. These results reveal a mechanistic link between chronic social isolation, metabolism, and sleep.

In a separate study we found that permeability of the BBB (blood–brain barrier)—the organ required for the maintenance of homeostatic levels of nutrients, ions, and other molecules in the brain—is modulated by sleep deprivation (SD). We observed increased BBB permeability in known sleep mutants as well as in acutely sleep-deprived wild type animals. Along with BBB permeability, RNA levels of the BBB master regulator moody are modulated by SD. Conversely, altering BBB permeability alone through glia-specific suppression of moody, gαo, loco, lachesin, or neuroglian—each a well-studied regulator of BBB function—was sufficient to induce robust sleep phenotypes. These studies demonstrate a potent role for the BBB in the regulation of sleep in Drosophila.

Host: Professor Per Svenningsson, per.svenningsson@ki.se

Contact: Pernilla Witte, Nobel Office, Nobel Forum, nobelforum@nobelprizemedicine.org