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. cv-c mutants exhibit decreased sleep time, diminished sleep rebound, and memory deficits comparable to those after sleep loss. Targeted ablation and rescue of Cv-c in sleep-control neurons of the dorsal FB impair and restore, respectively, normal sleep patterns. Sleep deprivation increases the excitability of dorsal FB neurons, but this homeostatic adjustment is disrupted in short-sleeping cv-c mutants. Sleep pressure thus shifts the input-output function of sleep-promoting neurons toward heightened activity by modulating ion channel function in a mechanism dependent on Cv-c.
•Insufficient sleep impairs the acquisition and consolidation of memories in the Drosophila Mushroom bodies.•Sleep may benefit memory-encoding circuits by homeostatically scaling synaptic ...connections.•Tools to control sleep timing in Drosophila may provide unique opportunities to study the cognitive benefits of sleep.
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. Because of the breadth and precision of available genetic tools, the fruit fly has become a powerful model system to understand sleep regulation and function. Importantly, these tools enable the dissection of memory-encoding circuits at the level of individual neurons, and have allowed the development of genetic tools to induce sleep on-demand. This review describes recent investigations of the role for sleep in memory using Drosophila and current hypotheses of sleep’s functions for supporting plasticity, learning, and memory.
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. Daytime sleep is elevated after antennal or wing injury, but sleep returns to baseline levels within 24 h after injury. Similar increases in sleep are not observed when olfactory receptor neurons are silenced or when other sensory organs are severed, suggesting that increased sleep after injury is not attributed to sensory deprivation, nociception, or generalized inflammatory responses. Neuroprotective disruptions of the E3 ubiquitin ligase highwire and c-Jun N-terminal kinase basket in olfactory receptor neurons weaken the sleep-promoting effects of antennal injury, suggesting that post-injury sleep may be influenced by the clearance of damaged neurons. Finally, we show that pre-synaptic active zones are preferentially removed from severed axons within hours after injury and that depriving recently injured flies of sleep slows the removal of both active zones and damaged axons. These data support a bidirectional interaction between sleep and synapse pruning after antennal injury: locally increasing the need to clear neural debris is associated with increased sleep, which is required for efficient active zone removal after injury.
•Sleep in Drosophila is temporarily increased following antennal removal•Increased sleep after injury can be attributed to neural damage•Sleep after injury promotes the removal of pre-synaptic proteins and axonal debris
Singh and Donlea find that severing the antennal nerves of the fruit fly acutely increases sleep. Sleep responses of injured flies can be weakened by manipulations that protect severed axons from removal. Sleep deprivation after injury slows the removal of neural debris from severed axons, indicating a role for sleep in recovery from neural damage.
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. Sleep changes caused by enhanced or diminished allatostatinergic transmission from dFB neurons and by inhibition or optogenetic stimulation of helicon cells support this notion. Helicon cells provide excitation to R2 neurons of the ellipsoid body, whose activity-dependent plasticity signals rising sleep pressure to the dFB. By virtue of this autoregulatory loop, dFB-mediated inhibition interrupts processes that incur a sleep debt, allowing restorative sleep to rebalance the books.
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•Sleep-promoting dFB neurons inhibit helicon cells of the central complex•Helicon cells transmit visual signals to R2 ring neurons and gate locomotion•Neurons generating sleep need and sleep-inducing neurons are recurrently connected•A unified mechanism accounts for sensory, motor, and homeostatic features of sleep
Neurons encoding sleep need and sleep-inducing neurons are recurrently connected. A crucial link in the circuit is necessary for visually guided movements but inhibited during sleep. A unified mechanism can thus account for sensory, motor, and homeostatic aspects of sleep.
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.
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.
•Amount of pre-synaptic BRP in mushroom bodies is inversely related to recent sleep•Increased BRP after sleep loss is restricted specifically to Kenyon cells•Outputs from KCs to different synaptic partners show varied changes with sleep loss
Weiss and Donlea find that sleep loss increases pre-synaptic Bruchpilot across the Drosophila mushroom body (MB) due to plasticity in MB-intrinsic Kenyon cells. Contacts from Kenyon cells to post-synaptic targets show differing changes with sleep loss, indicating that sleep deprivation may differentially alter distinct classes of MB synapses.
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.
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
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). Previous studies in both flies and mammals have implicated serotonin as an important neuromodulator of sleep, and our newly generated dSERT mutants show an increase in total sleep and altered sleep architecture that is mimicked by feeding the SSRI citalopram. Differences in daytime versus nighttime sleep architecture as well as genetic rescue experiments unexpectedly suggest that distinct serotonergic circuits may modulate daytime versus nighttime sleep. dSERT mutants also show defects in copulation and food intake, akin to the clinical side effects of SSRIs and consistent with the pleomorphic influence of serotonin on the behavior of D. melanogaster. Starvation did not overcome the sleep drive in the mutants and in male dSERT mutants, the drive to mate also failed to overcome sleep drive. dSERT may be used to further explore the mechanisms by which serotonin regulates sleep and its interplay with other complex behaviors.
Highlights • Potassium channel dynamics control excitability of sleep-promoting neurons in flies. • The Drosophila ellipsoid body and dorsal fan-shaped body interact to drive sleep homeostasis. • ...Astrocyte-derived adenosine links cellular metabolism and sleep homeostasis in rodents. • Adenosine both suppresses wake-promoting neuronal systems and excites sleep promoting neurons. • Opponent actions of wake-promoting and sleep promoting neurons occur in flies and rodents.
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