Event:

Sleep is universal among animals with a nervous system, and homeostatically regulated, yet its controlled variable is poorly defined. Understanding sleep homeostasis requires identifying how sleep need is represented internally, which outputs trigger recovery sleep, and the mechanisms that generate and regulate them. Using Drosophila, I address these questions in a genetically tractable sleep-control neuronal population.
We profiled single-cell transcriptomes of neurons projecting to the dorsal fan-shaped body (dFBNs), a core sleep homeostatic centre. Sleep loss upregulates genes for aerobic energy metabolism and downregulates genes encoding presynaptic machinery, revealing cell-intrinsic and network-level signatures of deprivation.
This transcriptional reprogramming coincides with organelle-level remodelling: mitochondrial fission, increased mitophagy and more contacts between mitochondria and endoplasmic reticulum. Inducing fission reduces sleep and neuronal excitability; promoting fusion has opposite effects. Rescuing these changes by consuming ATP or by imposing electron overflow in the respiratory chain implicates mitochondrial electron leak as the trigger. During sleep loss, wake-promoting dopamine inhibits dFBNs, creating an electron surplus and elevated ATP levels. Bypassing the electron transport chain with a light-driven mitochondrial proton pump promotes sleep by mismatching ATP demand and electron flux, supporting a mitochondria-mediated feedback loop that bidirectionally links ATP levels to neuronal excitability and sleep.
dFBNs convey this intrinsic signal via population dynamics. In vivo patch clamp and calcium imaging reveal delta-band slow-wave oscillations whose power scales with sleep need and whose optogenetic replay promotes sleep. These rhythms arise from interhemispheric competition between two mutually inhibitory half-centres that oscillate in antiphase and require homeostatic depression of efferent synapses. This motif, widely used for locomotion, here regulates a function beyond motor control.
I will place this neuroenergetic feedback mechanism into the wider context of analogous homeostatic systems, such as the mitochondrial control of hunger-promoting neurons in the mammalian hypothalamus, and cortical oscillations and mitochondrial rearrangements in sleeping vertebrates.