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

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 mushroom body (MB), but not in other classes of MB neurons.

Examining Sleep Modulation by Ellipsoid Body Neurons.

Recent work in has uncovered several neighboring classes of sleep-regulatory neurons within the central complex. However, the logic of connectivity and network motifs remains limited by the incomplete examination of relevant cell types. Using a recent genetic-anatomic classification of ellipsoid body ring neurons, we conducted a thermogenetic screen in female flies to assess sleep/wake behavior and identified two wake-promoting drivers that label ER3d neurons and two sleep-promoting drivers that express in ER3m cells.

Sleep sculpts circuits in every species studied.

In this issue of Cell, we see first evidence of sleep-dependent circuit remodeling alongside behavioral memory consolidation in C. elegans. Examining memory of a never-rewarded odor during post-training sleep from synapse to behavior all in one organism opens the opportunity to use this well-mapped nervous system to study mechanisms of sleep-dependent memory consolidation.

Mutation of the Drosophila melanogaster serotonin transporter dSERT impacts sleep, courtship, and feeding behaviors.

The Serotonin Transporter (SERT) regulates extracellular serotonin levels and is the target of most current drugs used to treat depression. The mechanisms by which inhibition of SERT activity influences behavior are poorly understood. To address this question in the model organism Drosophila melanogaster, we developed new loss of function mutations in Drosophila SERT (dSERT).

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.

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).

Bidirectional Regulation of Sleep and Synapse Pruning after Neural Injury.

Following acute neural injury, severed axons undergo programmed Wallerian degeneration over several following days. While sleep has been linked with synaptic reorganization under other conditions, the role of sleep in responses to neural injuries remains poorly understood. To study the relationship between sleep and neural injury responses, we examined Drosophila melanogaster following the removal of antennae or other sensory tissues.

Neuronal Constituents and Putative Interactions Within the Ellipsoid Body Neuropil.

The central complex (CX) is a midline-situated collection of neuropil compartments in the arthropod central brain, implicated in higher-order processes such as goal-directed navigation. Here, we provide a systematic genetic-neuroanatomical analysis of the ellipsoid body (EB), a compartment which represents a major afferent portal of the CX. The neuropil volume of the EB, along with its prominent input compartment, called the bulb, is subdivided into precisely tessellated domains, distinguishable based on intensity of the global marker DN-cadherin.

Temporal Coding of Sleep.

In Drosophila, well-delineated circuits control circadian rhythms, but the electrophysiological patterns that occur within these circuits are not well understood. In this issue, Tabuchi et al. clarify the temporal coding within a circuit, linking patterns of neural activity to sleep behavior.

Roles for sleep in memory: insights from the fly.

Sleep has been universally conserved across animal species. The basic functions of sleep remain unclear, but insufficient sleep impairs memory acquisition and retention in both vertebrates and invertebrates. Sleep is also a homeostatic process that is influenced not only by the amount of time awake, but also by neural activity and plasticity.

Recurrent Circuitry for Balancing Sleep Need and Sleep.

Sleep-promoting neurons in the dorsal fan-shaped body (dFB) of Drosophila are integral to sleep homeostasis, but how these cells impose sleep on the organism is unknown. We report that dFB neurons communicate via inhibitory transmitters, including allatostatin-A (AstA), with interneurons connecting the superior arch with the ellipsoid body of the central complex. These "helicon cells" express the galanin receptor homolog AstA-R1, respond to visual input, gate locomotion, and are inhibited by AstA, suggesting that dFB neurons promote rest by suppressing visually guided movement.

Neuronal and molecular mechanisms of sleep homeostasis.

Sleep is necessary for survival, and prolonged waking causes a homeostatic increase in the need for recovery sleep. Homeostasis is a core component of sleep regulation and has been tightly conserved across evolution from invertebrates to man. Homeostatic sleep regulation was first identified among insects in cockroaches several decades ago, but the characterization of sleep rebound in Drosophila melanogaster opened the use of insect model species to understand homeostatic functions and regulation of sleep.

Neuronal substrates of sleep homeostasis; lessons from flies, rats and mice.

Sleep homeostasis is a fundamental property of vigilance state regulation that is highly conserved across species. Neuronal systems and circuits that underlie sleep homeostasis are not well understood. In Drosophila, a neuronal circuit involving neurons in the ellipsoid body and in the dorsal Fan-shaped body is a candidate for both tracing sleep need during waking and translating it to increased sleep drive and expression.

Operation of a homeostatic sleep switch.

Sleep disconnects animals from the external world, at considerable risks and costs that must be offset by a vital benefit. Insight into this mysterious benefit will come from understanding sleep homeostasis: to monitor sleep need, an internal bookkeeper must track physiological changes that are linked to the core function of sleep. In Drosophila, a crucial component of the machinery for sleep homeostasis is a cluster of neurons innervating the dorsal fan-shaped body (dFB) of the central complex.

Genetic rescue of functional senescence in synaptic and behavioral plasticity.

Study Objectives: Aging has been linked with decreased neural plasticity and memory formation in humans and in laboratory model species such as the fruit fly, Drosophila melanogaster. Here, we examine plastic responses following social experience in Drosophila as a high-throughput method to identify interventions that prevent these impairments.

Patients Or Participants: Wild-type and transgenic Drosophila melanogaster.

Neuronal machinery of sleep homeostasis in Drosophila.

Sleep is under homeostatic control, but the mechanisms that sense sleep need and correct sleep deficits remain unknown. Here, we report that sleep-promoting neurons with projections to the dorsal fan-shaped body (FB) form the output arm of Drosophila's sleep homeostat. Homeostatic sleep control requires the Rho-GTPase-activating protein encoded by the crossveinless-c (cv-c) gene in order to transduce sleep pressure into increased electrical excitability of dorsal FB neurons.

Foraging alters resilience/vulnerability to sleep disruption and starvation in Drosophila.

Recent human studies suggest that genetic polymorphisms allow an individual to maintain optimal cognitive functioning during sleep deprivation. If such polymorphisms were not associated with additional costs, selective pressures would allow these alleles to spread through the population such that an evolutionary alternative to sleep would emerge. To determine whether there are indeed costs associated with resiliency to sleep loss, we challenged natural allelic variants of the foraging gene (for) with either sleep deprivation or starvation.

Inducing sleep by remote control facilitates memory consolidation in Drosophila.

Sleep is believed to play an important role in memory consolidation. We induced sleep on demand by expressing the temperature-gated nonspecific cation channel Transient receptor potential cation channel (UAS-TrpA1) in neurons, including those with projections to the dorsal fan-shaped body (FB). When the temperature was raised to 31°C, flies entered a quiescent state that meets the criteria for identifying sleep.

Sleeping together using social interactions to understand the role of sleep in plasticity.

Social experience alters the expression of genes related to synaptic function and plasticity, induces elaborations in the morphology of neural structures throughout the brain (Volkmar and Greenough, 1972; Greenough et al., 1978; Technau, 2007), improves cognitive and behavioral performance (Pham et al., 1999a; Toscano et al.

Use-dependent plasticity in clock neurons regulates sleep need in Drosophila.

Sleep is important for memory consolidation and is responsive to waking experience. Clock circuitry is uniquely positioned to coordinate interactions between processes underlying memory and sleep need. Flies increase sleep both after exposure to an enriched social environment and after protocols that induce long-term memory.