Sleep deprivation drives brain-wide changes in cholinergic presynapse abundance in Drosophila melanogaster.

Sleep is an evolutionarily conserved state that supports brain functions, including synaptic plasticity, in species across the animal kingdom. Here, we examine the neuroanatomical and cell-type distribution of presynaptic scaling in the fly brain after sleep loss. We previously found that sleep loss drives accumulation of the active zone scaffolding protein Bruchpilot (BRP) within cholinergic Kenyon cells of the Drosophila melanogaster mushroom body (MB), but not in other classes of MB neurons. To test whether similar cell type-specific trends in plasticity occur broadly across the brain, we used a flp-based genetic reporter to label presynaptic BRP in cholinergic, dopaminergic, GABAergic, or glutamatergic neurons. We then collected whole-brain confocal image stacks of BRP intensity to systematically quantify BRP, a marker of presynapse abundance, across 37 neuropil regions of the central fly brain. Our results indicate that sleep loss, either by overnight (12-h) mechanical stimulation or chronic sleep disruption in insomniac mutants, broadly elevates cholinergic synapse abundance across the brain, while synapse abundance in neurons that produce other neurotransmitters undergoes weaker, if any, changes. Extending sleep deprivation to 24 h drives brain-wide upscaling in glutamatergic, but not other, synapses. Finally, overnight male-male social pairings induce increased BRP in excitatory synapses despite male-female pairings eliciting more waking activity, suggesting experience-specific plasticity. Within neurotransmitter class and waking context, BRP changes are similar across the 37 neuropil domains, indicating that similar synaptic scaling rules may apply across the brain during acute sleep loss and that sleep need may broadly alter excitatory-inhibitory balance in the central brain.

Sleep deprivation results in diverse patterns of synaptic scaling across the Drosophila mushroom bodies.

Sleep is essential for a variety of plastic processes, including learning and memory. However, the consequences of insufficient sleep on circuit connectivity remain poorly understood. To better appreciate the effects of sleep loss on synaptic connectivity across a memory-encoding circuit, we examined changes in the distribution of synaptic markers in the Drosophila mushroom body (MB). Protein-trap tags for active zone components indicate that recent sleep time is inversely correlated with Bruchpilot (BRP) abundance in the MB lobes; sleep loss elevates BRP while sleep induction reduces BRP across the MB. Overnight sleep deprivation also elevated levels of dSyd-1 and Cacophony, but not other pre-synaptic proteins. Cell-type-specific genetic reporters show that MB-intrinsic Kenyon cells (KCs) exhibit increased pre-synaptic BRP throughout the axonal lobes after sleep deprivation; similar increases were not detected in projections from large interneurons or dopaminergic neurons that innervate the MB. These results indicate that pre-synaptic plasticity in KCs is responsible for elevated levels of BRP in the MB lobes of sleep-deprived flies. Because KCs provide synaptic inputs to several classes of post-synaptic partners, we next used a fluorescent reporter for synaptic contacts to test whether each class of KC output connections is scaled uniformly by sleep loss. The KC output synapses that we observed here can be divided into three classes: KCs to MB interneurons; KCs to dopaminergic neurons; and KCs to MB output neurons. No single class showed uniform scaling across each constituent member, indicating that different rules may govern plasticity during sleep loss across cell types.

Roles for Sleep in Neural and Behavioral Plasticity: Reviewing Variation in the Consequences of Sleep Loss.

Sleep is a vital physiological state that has been broadly conserved across the evolution of animal species. While the precise functions of sleep remain poorly understood, a large body of research has examined the negative consequences of sleep loss on neural and behavioral plasticity. While sleep disruption generally results in degraded neural plasticity and cognitive function, the impact of sleep loss can vary widely with age, between individuals, and across physiological contexts. Additionally, several recent studies indicate that sleep loss differentially impacts distinct neuronal populations within memory-encoding circuitry. These findings indicate that the negative consequences of sleep loss are not universally shared, and that identifying conditions that influence the resilience of an organism (or neuron type) to sleep loss might open future opportunities to examine sleep's core functions in the brain. Here, we discuss the functional roles for sleep in adaptive plasticity and review factors that can contribute to individual variations in sleep behavior and responses to sleep loss.