Tracking sleepiness in the fly brain [with video]

Sleep is under homeostatic control, but the neural mechanisms that sense the need to sleep remain poorly understood. We have found that a small cluster of sleep-promoting neurons in the fly brain becomes more excitable after extended waking to allow the brain to regain lost sleep and restore neural functioning.

HFSP Long-Term Fellow Jeffrey Donlea and colleagues
authored on Mon, 14 April 2014

Sleep is a behavioral state that has been broadly conserved across evolution from invertebrates to humans. Despite decades of study, however, the basic biological functions of sleep remain unidentified. It is thought that two processes influence sleep in most animals: the circadian clock, which allows the coordination of sleep patterns with daily sunlight schedules, and a sleep homeostat, which monitors and corrects sleep deficits incurred during prolonged waking. The identification of the molecular oscillators that underlie circadian rhythmicity has been one of the great successes of behavioral genetics. In contrast, little is known about either the biological functions or neural circuits that underpin sleep homeostasis.

In our recent paper in Neuron, we describe how a discrete cluster of sleep-promoting neurons that project into the dorsal Fan-shaped Body (FB) act as an important component of the Drosophila sleep homeostat. Disrupting a single gene, crossveinless-c (cv-c), in these neurons abrogates the homeostatic response to sleep loss and induces insomnia-like symptoms – flies without cv-c lose sleep that they need and exhibit memory deficits as a result. We used whole-cell recordings to understand how dorsal FB neurons might represent sleep need and found that these neurons became more electrically excitable following sleep loss and less responsive after recovery sleep. In short-sleeping cv-c mutants the baseline responsiveness of dorsal FB neurons was dramatically reduced, and the increase in responsiveness that is normally caused by sleep loss was absent. Because activity of dorsal FB neurons is, in itself, sufficient to induce sleep, this modulation of excitability may be a core mechanism of the homeostatic sleep switch.

Our results suggest that homeostatic sleep drive might be represented by changes in the intrinsic excitability of small groups of sleep-control neurons and not necessarily by synaptic weight changes that are distributed across larger neural networks. What might be the role of Cv-c, a Rho GTPase activating protein, in the regulation of dorsal FB excitability? Several small GTPases of the Rho family have been implicated in the modulation of ion channels—a process whose disruption in cv-c mutants we observe electrophysiologically. While our paper provides a novel physiological model for the representation of sleep need, future studies will be needed to fully understand this mechanism. By identifying the changes that occur during waking to activate the sleep homeostat, we might also move closer to solving the mystery of why animals need sleep to survive.

Reference

Neuronal machinery of sleep homeostasis in Drosophila.  Donlea JM*, Pimentel D*, Miesenböck G. Neuron. 2014 Feb 19: 81, 860–872.

Pubmed link

Link to article (open access)