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Sleep is regulated by many environmental factors including food availability and exposure to sensory stimuli. A recent study identifies a gut-brain axis that is activated by dietary proteins and inhibits sensory responsiveness, allowing animals to enter and maintain deep sleep., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Regulation of water intake is governed by numerous motivated behaviors that are critical for the survival of nearly all animals. A recent study identifies a critical role for glia-neuron communication in the detection of water shortage and the initiation of thirst-associated behaviors., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Sensory systems display remarkable plasticity and are under strong evolutionary selection. The Mexican cavefish, Astyanax mexicanus, consists of eyed river-dwelling surface populations and multiple independent cave populations that have converged on eye loss, providing the opportunity to examine the evolution of sensory circuits in response to environmental perturbation. Functional analysis across multiple transgenic populations expressing GCaMP6s showed that functional connectivity of the optic tectum largely did not differ between populations, except for the selective loss of negatively correlated activity within the cavefish tectum, suggesting positively correlated neural activity is resistant to an evolved loss of input from the retina. Furthermore, analysis of surface-cave hybrid fish reveals that changes in the tectum are genetically distinct from those encoding eye loss. Together, these findings uncover the independent evolution of multiple components of the visual system and establish the use of functional imaging in A. mexicanus to study neural circuit evolution., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Adaptation to novel environments often involves the evolution of multiple morphological, physiological, and behavioral traits. One striking example of multi-trait evolution is the suite of traits that has evolved repeatedly in cave animals, including regression of eyes, loss of pigmentation, and enhancement of non-visual sensory systems. 1 , 2 The Mexican tetra, Astyanax mexicanus, consists of fish that inhabit at least 30 caves in Mexico and ancestral-like surface fish that inhabit the rivers of Mexico and southern Texas. 3 Cave A. mexicanus are interfertile with surface fish and have evolved a number of traits, including reduced pigmentation, eye loss, and alterations to behavior. 4-6 To define relationships between different cave-evolved traits, we phenotyped 208 surface-cave F2 hybrid fish for numerous morphological and behavioral traits. We found differences in sleep between pigmented and albino hybrid fish, raising the possibility that these traits share a genetic basis. In cavefish and other species, mutations in oculocutaneous albinism 2 (oca2) cause albinism. 7-12 Surface fish with mutations in oca2 displayed both albinism and reduced sleep. Further, this mutation in oca2 fails to complement sleep loss when surface fish harboring this engineered mutation are crossed to independently evolved populations of albino cavefish with naturally occurring mutations in oca2. Analysis of the oca2 locus in wild-caught cave and surface fish suggests that oca2 is under positive selection in 3 cave populations. Taken together, these findings identify oca2 as a novel regulator of sleep and suggest that a pleiotropic function of oca2 underlies the adaptive evolution of albinism and sleep loss., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Sleep is critical for diverse aspects of brain function in animals ranging from invertebrates to humans. Powerful genetic tools in the fruit fly Drosophila melanogaster have identified - at an unprecedented level of detail - genes and neural circuits that regulate sleep. This research has revealed that the functions and neural principles of sleep regulation are largely conserved from flies to mammals. Further, genetic approaches to studying sleep have uncovered mechanisms underlying the integration of sleep and many different biological processes, including circadian timekeeping, metabolism, social interactions, and aging. These findings show that in flies, as in mammals, sleep is not a single state, but instead consists of multiple physiological and behavioral states that change in response to the environment, and is shaped by life history. Here, we review advances in the study of sleep in Drosophila, discuss their implications for understanding the fundamental functions of sleep that are likely to be conserved among animal species, and identify important unanswered questions in the field., (Copyright © 2020. Published by Elsevier Inc.)

Chronic sleep disturbance is associated with numerous health consequences, including neurodegenerative disease and cognitive decline [1]. Neurite damage due to apoptosis, trauma, or genetic factors is a common feature of aging, and clearance of damaged neurons is essential for maintenance of brain function. In the central nervous system, damaged neurites are cleared by Wallerian degeneration, in which activated microglia and macrophages engulf damaged neurons [2]. The fruit fly Drosophila melanogaster provides a powerful model for investigating the relationship between sleep and Wallerian degeneration [3]. Several lines of evidence suggest that glia influence sleep duration, sleep-mediated neuronal homeostasis, and clearance of toxic substances during sleep, raising the possibility that glial engulfment of damaged axons is regulated by sleep [4]. To explore this possibility, we axotomized olfactory receptor neurons and measured the effects of sleep loss or gain on the clearance of damaged neurites. Mechanical and genetic sleep deprivation impaired the clearance of damaged neurites. Conversely, treatment with the sleep-promoting drug gaboxadol accelerated clearance, while genetic induction of sleep promotes Draper expression. In sleep-deprived animals, multiple markers of glial activation were delayed, including activation of the JAK-STAT pathway, upregulation of the cell corpse engulfment receptor Draper, and innervation of the antennal lobe by glial membranes. These markers were all enhanced following genetic and pharmacological sleep induction. Taken together, these findings reveal a critical association between sleep and glial activation following neural injury, providing a platform for further investigations of the molecular mechanisms underlying sleep-dependent modulation of glial function and neurite clearance., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Sleep is critical for many aspects of brain function and is accompanied by brain-wide changes in the physiology of neurons and synapses [1, 2]. Growing evidence suggests that glial cells contribute to diverse aspects of sleep regulation, including neuronal and metabolic homeostasis [3-5], although the molecular basis for this remains poorly understood. The fruit fly, Drosophila melanogaster, displays all the behavioral and physiological characteristics of sleep [1, 2], and genetic screening in flies has identified both conserved and novel regulators of sleep and wakefulness [2, 6, 7]. With this approach, we identified Excitatory amino acid transporter 2 (Eaat2) and found that its loss from glia, but not neurons, increases sleep. We show that Eaat2 is expressed in ensheathing glia, where Eaat2 functions during adulthood to regulate sleep. Increased sleep in Eaat2-deficient flies is accompanied by reduction of metabolic rate during sleep bouts, an indicator of deeper sleep intensity. Eaat2 is a member of the conserved EAAT family of membrane transport proteins [8], raising the possibility that it affects sleep by controlling the movement of ions and neuroactive chemical messengers to and from ensheathing glia. In vitro, Eaat2 is a transporter of taurine [9], which promotes sleep when fed to flies [10]. We find that the acute effect of taurine on sleep is abolished in Eaat2 mutant flies. Together, these findings reveal a wake-promoting role for Eaat2 in ensheathing glia through a taurine-dependent mechanism., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

A new study in the fruit fly, Drosophila melanogaster, has identified a neural circuitry that connects regions that control sleep with those that encode sleep pressure. These novel cells, termed helicon cells for their unique morphology, are modulated by sleep control centers and integrate sensory information, providing a novel mechanism for gating of sleep., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Dysregulation of sleep or feeding has enormous health consequences. In humans, acute sleep loss is associated with increased appetite and insulin insensitivity, while chronically sleep-deprived individuals are more likely to develop obesity, metabolic syndrome, type II diabetes, and cardiovascular disease. Conversely, metabolic state potently modulates sleep and circadian behavior; yet, the molecular basis for sleep-metabolism interactions remains poorly understood. Here, we describe the identification of translin (trsn), a highly conserved RNA/DNA binding protein, as essential for starvation-induced sleep suppression. Strikingly, trsn does not appear to regulate energy stores, free glucose levels, or feeding behavior suggesting the sleep phenotype of trsn mutant flies is not a consequence of general metabolic dysfunction or blunted response to starvation. While broadly expressed in all neurons, trsn is transcriptionally upregulated in the heads of flies in response to starvation. Spatially restricted rescue or targeted knockdown localizes trsn function to neurons that produce the tachykinin family neuropeptide Leucokinin. Manipulation of neural activity in Leucokinin neurons revealed these neurons to be required for starvation-induced sleep suppression. Taken together, these findings establish trsn as an essential integrator of sleep and metabolic state, with implications for understanding the neural mechanism underlying sleep disruption in response to environmental perturbation., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Sleep is thought to be controlled by two main processes: a circadian clock that primarily regulates sleep timing and a homeostatic mechanism that detects and responds to sleep need. Whereas abundant experimental evidence suggests that sleep need increases with time spent awake, the contributions of different brain arousal systems have not been assessed independently of each other to determine whether certain neural circuits, rather than waking per se, selectively contribute to sleep homeostasis. Using the fruit fly, Drosophila melanogaster, we found that sustained thermogenetic activation of three independent neurotransmitter systems promoted nighttime wakefulness. However, only sleep deprivation resulting from activation of cholinergic neurons was sufficient to elicit subsequent homeostatic recovery sleep, as assessed by multiple behavioral criteria. In contrast, sleep deprivation resulting from activation of octopaminergic neurons suppressed homeostatic recovery sleep, indicating that wakefulness can be dissociated from accrual of sleep need. Neurons that promote sleep homeostasis were found to innervate the central brain and motor control regions of the thoracic ganglion. Blocking activity of these neurons suppressed recovery sleep but did not alter baseline sleep, further differentiating between neural control of sleep homeostasis and daily fluctuations in the sleep/wake cycle. Importantly, selective activation of wake-promoting neurons without engaging the sleep homeostat impaired subsequent short-term memory, thus providing evidence that neural circuits that regulate sleep homeostasis are important for behavioral plasticity. Together, our data suggest a neural circuit model involving distinct populations of wake-promoting neurons, some of which are involved in homeostatic control of sleep and cognition., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Taste memories allow animals to modulate feeding behavior in accordance with past experience and avoid the consumption of potentially harmful food [1]. We have developed a single-fly taste memory assay to functionally interrogate the neural circuitry encoding taste memories [2]. Here, we screen a collection of Split-GAL4 lines that label small populations of neurons associated with the fly memory center-the mushroom bodies (MBs) [3]. Genetic silencing of PPL1 dopamine neurons disrupts conditioned, but not naive, feeding behavior, suggesting these neurons are selectively involved in the conditioned taste response. We identify two PPL1 subpopulations that innervate the MB α lobe and are essential for aversive taste memory. Thermogenetic activation of these dopamine neurons during training induces memory, indicating these neurons are sufficient for the reinforcing properties of bitter tastant to the MBs. Silencing of either the intrinsic MB neurons or the output neurons from the α lobe disrupts taste conditioning. Thermogenetic manipulation of these output neurons alters naive feeding response, suggesting that dopamine neurons modulate the threshold of response to appetitive tastants. Taken together, these findings detail a neural mechanism underlying the formation of taste memory and provide a functional model for dopamine-dependent plasticity in Drosophila., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A new study in fruit flies suggests modulation of neural activity links sleep and Alzheimer's disease. Both sleep loss and amyloid beta increase neural excitability, which reinforces the accumulation of amyloid beta and shortens lifespan., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A new study has identified a neural circuit that is responsible for increasing sleep in young fruit flies. Reduced dopamine signaling to the fan-shaped body during early life promotes sleep and is critical for proper brain development., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A new study examining the neural circuitry regulating sleep in Drosophila has identified a pair of dopamine neurons that signal to the fan-shaped body to suppress sleep. These neurons are separate from the dopamine neurons that regulate motivation, memory, and feeding, suggesting that independent populations of dopamine neurons regulate distinct behaviors., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Patterns of sleep vary widely among species, but the functional and evolutionary principles responsible for this diversity remain unknown. The characin fish, Astyanax mexicanus, has eyed surface and numerous blind cave populations. The cave populations are largely independent in their origins, and the species is ideal for studying the genetic bases of convergent evolution. Here we show that this system is also uniquely valuable for the investigation of variability in patterns of sleep. We find that a clearly defined change in ecological conditions, from surface to cave, is correlated with a dramatic reduction in sleep in three independently derived cave populations of A. mexicanus. Analyses of surface × cave hybrids show that the alleles for reduced sleep in the Pachón and Tinaja cave populations are dominant in effect to the surface alleles. Genetic analysis of hybrids between surface and Pachón cavefish suggests that only a small number of loci with dominant effects are involved. Our results demonstrate that sleep is an evolutionarily labile phenotype, highly responsive to changes in ecological conditions. To our knowledge, this is the first example of a single species with a convergence on sleep loss exhibited by several independently evolved populations correlated with population-specific ecologies., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Neural systems controlling the vital functions of sleep and feeding in mammals are tightly interconnected: sleep deprivation promotes feeding, whereas starvation suppresses sleep. Here we show that starvation in Drosophila potently suppresses sleep, suggesting that these two homeostatically regulated behaviors are also integrated in flies. The sleep-suppressing effect of starvation is independent of the mushroom bodies, a previously identified sleep locus in the fly brain, and therefore is regulated by distinct neural circuitry. The circadian clock genes Clock (Clk) and cycle (cyc) are critical for proper sleep suppression during starvation. However, the sleep suppression is independent of light cues and of circadian rhythms as shown by the fact that starved period mutants sleep like wild-type flies. By selectively targeting subpopulations of Clk-expressing neurons, we localize the observed sleep phenotype to the dorsally located circadian neurons. These findings show that Clk and cyc act during starvation to modulate the conflict of whether flies sleep or search for food., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Memories are formed, stabilized in a time-dependent manner, and stored in neural networks. In Drosophila, retrieval of punitive and rewarded odor memories depends on output from mushroom body (MB) neurons, consistent with the idea that both types of memory are represented there. Dorsal Paired Medial (DPM) neurons innervate the mushroom bodies, and DPM neuron output is required for the stability of punished odor memory. Here we show that stable reward-odor memory is also DPM neuron dependent. DPM neuron expression of amnesiac (amn) in amn mutant flies restores wild-type memory. In addition, disrupting DPM neurotransmission between training and testing abolishes reward-odor memory, just as it does with punished memory. We further examined DPM-MB connectivity by overexpressing a DScam variant that reduces DPM neuron projections to the MB alpha, beta, and gamma lobes. DPM neurons that primarily project to MB alpha' and beta' lobes are capable of stabilizing punitive- and reward-odor memory, implying that both forms of memory have similar circuit requirements. Therefore, our results suggest that the fly employs the local DPM-MB circuit to stabilize punitive- and reward-odor memories and that stable aspects of both forms of memory may reside in mushroom body alpha' and beta' lobe neurons.

Dopamine-containing neurons are widespread in the fly brain and have been implicated in negatively reinforced memory. Current technology allows the investigator to watch dopaminergic neurons in action in the brain of a learning fly.