Biology subjects

van Swinderen, B.

Publications and source records attributed to van Swinderen, B..

13 recordsLinked to original sources

bioRxiv2025

Long-term multichannel recordings in Drosophila flies reveal distinct responses to deviant visual stimuli during sleep compared to wake

During sleep, behavioral responsiveness to external stimuli is decreased. This classical definition of sleep has been applied effectively across the animal kingdom to identify this common behavioral state in a growing list of creatures, from mammals to invertebrates. Yet it remains unclear whether decreased behavioral responsiveness during sleep is necessarily associated with decreased responsiveness in brain activity, especially in relative latecomers to the sleep field, such as insects. Here, we perform long-term multichannel electrophysiology in tethered Drosophila melanogaster flies exposed continuously to flashing visual stimuli. Flies were still able to sleep under these visual stimulation conditions, as determined by traditional immobility duration criteria for the field. Interestingly, local field potentials (LFPs) recorded in a transect through the fly brain failed to show any difference in amplitude during sleep compared to wake when the visual stimuli were invariant. In contrast, LFP responses were lower when visual stimuli were variable and of lower probability, especially in the central brain. Central brain responses to deviant stimuli were lowest during the deepest stage of sleep, characterized by more regular proboscis extensions. This shows that the sleeping fly brain processes low-probability visual stimuli in a different way than more repeated stimuli and presents Drosophila as a model system for studying the potential role of sleep in regulating predictive processing. SUMMARY STATEMENTThe sleeping fly brain still responds to visual stimuli. However, response amplitudes depend on stimulus history and probability, as well as recording location.

neuroscience↗

bioRxiv2024

Breaking free from the clocks tyranny restores memory to brain damaged flies

The relationship between sleep and memory is an active topic of investigation. In this context, we demonstrate that enhancing sleep restores memory to flies with ablated Mushroom Bodies (MB), a key memory center; this is consistent across several memory assays. Mapping the underlying circuitry reveals circadian modulation of a subset of Dopaminergic neurons (DANs) that modulate aversive learning. Using imaging, we show that MB-ablation disrupts, and sleep restores the time of day these neurons are most responsive. Knocking down the receptor for the clock output signal, Pigment-dispersing factor (Pdfr), in this subset of DANs restores memory to MB-ablated flies. Crucially, MB-ablation does not result in memory impairments in the absence of a functioning clock. Our results reveal neuromodulations key role in cognitive restoration, where sleep aids memory in damaged brains, but a functioning clock unexpectedly hinders this process.

neuroscience↗

bioRxiv2023

Multivariate classification of multichannel long-term electrophysiology data identifies different sleep stages in fruit flies

Sleep is observed in most animals, which suggests it subserves a fundamental process associated with adaptive biological functions. However, the evidence to directly associate sleep with a specific function is lacking, in part because sleep is not a single process in many animals. In humans and other mammals, different sleep stages have traditionally been identified using electroencephalograms (EEGs), but such an approach is not feasible in different animals such as insects. Here, we perform long-term multichannel local field potential (LFP) recordings in the brains of behaving flies undergoing spontaneous sleep bouts. We developed protocols to allow for consistent spatial recordings of LFPs across multiple flies, allowing us to compare the LFP activity across awake and sleep periods and further compare the same to induced sleep. Using machine learning, we uncover the existence of distinct temporal stages of sleep and explore the associated spatial and spectral features across the fly brain. Further, we analyze the electrophysiological correlates of micro-behaviours associated with certain sleep stages. We confirm the existence of a distinct sleep stage associated with rhythmic proboscis extensions and show that spectral features of this sleep-related behavior differ significantly from those associated with the same behavior during wakefulness, indicating a dissociation between behavior and the brain states wherein these behaviors reside.

neuroscience↗

bioRxiv2023

Experimentally induced active and quiet sleep engage non-overlapping transcriptomes in Drosophila

Sleep in mammals can be broadly classified into two different physiological categories: rapid eye movement (REM) sleep and slow wave sleep (SWS), and accordingly REM and SWS are thought to achieve a different set of functions. The fruit fly Drosophila melanogaster is increasingly being used as a model to understand sleep functions, although it remains unclear if the fly brain also engages in different kinds of sleep as well. Here, we compare two commonly used approaches for studying sleep experimentally in Drosophila: optogenetic activation of sleep-promoting neurons and provision of a sleep-promoting drug, Gaboxadol. We find that these different sleep-induction methods have similar effects on increasing sleep duration, but divergent effects on brain activity. Transcriptomic analysis reveals that drug-induced deep sleep ( quiet sleep) mostly downregulates metabolism genes, whereas optogenetic active sleep upregulates a wide range of genes relevant to normal waking functions. This suggests that optogenetics and pharmacological induction of sleep in Drosophila promote different features of sleep, which engage different sets of genes to achieve their respective functions.

neuroscience↗

bioRxiv2023

Synapse-specific trapping of Syntaxin1a into nanoclusters by the general anesthetic isoflurane

General anesthetics disrupt brain network dynamics through multiple pathways, predominately through post-synaptic potentiation of GABAAR and pre-synaptic inhibition of neuroexocytosis. Common clinical general anesthetic drugs, such as propofol and isoflurane, have been shown to interact and interfere with a core component of the exocytic release machinery, Syntaxin1A, to cause impaired neurotransmitter release. Recent in vitro studies however suggest that these drugs to not affect all synapse subtypes equally. We investigated the role of Syntaxin1A in multiple neurotransmitter systems under isoflurane general anesthesia in the adult Drosophila brain using live-cell super resolution microscopy and optogenetic readouts of exocytosis. We found that effects of isoflurane anesthesia were neuron specific and only impaired Syntaxin1A activity in excitatory neurons at cholinergic synapses, but not inhibitory GABAergic or glutamatergic neurons. These results indicate that general anesthetics could work by producing successive bouts of inhibition across the brain, by reducing neuroexocytosis from excitatory neurons specifically as well as silencing arousal systems through GABAAR potentiation.

neuroscience↗

bioRxiv2021

Sleep promoting neurons remodel their response properties to calibrate sleep drive with environmental demands.

Falling asleep at the wrong time can place an individual at risk of immediate physical harm. However, not sleeping degrades cognition and adaptive behavior. To understand how animals match sleep need with environmental demands, we used live-brain imaging to examine the physiological response properties of the Drosophila sleep homeostat (dFB) following interventions that modify sleep (sleep deprivation, starvation, time-restricted feeding, memory consolidation). We report that dFB neurons can distinguish between different types of waking and can change their physiological response-properties accordingly. That is, dFB neurons are not simply passive components of a hard-wired circuit. Rather, the dFB neurons themselves can determine their response to the activity from upstream circuits. Finally, we show that the dFB appears to contain a memory trace of prior exposure to metabolic challenges induced by starvation or time-restricted feeding. Together these data highlight that the sleep homeostat is plastic and suggests an underlying mechanism.

neuroscience↗

bioRxiv2020

Tracking single molecule dynamics in the anesthetized Drosophila brain

Super-resolution microscopy provides valuable insight for understanding the nanoscale organization within living tissue, although this method is typically restricted to cultured or dissociated cells. Here, we develop a method to track the mobility of individual proteins in ex vivo adult Drosophila melanogaster brains, focusing on a key component of the presynaptic release machinery, syntaxin1A. We show that individual syntaxin1A dynamics can be reliably tracked within neurons in the whole fly brain, and that the mobility of syntaxin1A molecules increases following conditional neural stimulation. We then apply this preparation to the problem of general anesthesia, to address how different anesthetics might affect single molecule dynamics in intact brain synapses. We find that propofol, etomidate, and isoflurane significantly impair syntaxin1A mobility, while ketamine and sevoflurane have little effect. Resolving single molecule dynamics in intact fly brains provides a novel approach to link localized molecular effects with systems-level phenomena such as general anesthesia. Impact statementA new approach to track the mobility of individual molecules using intact fly brains reveals a common presynaptic effect for different intravenous and volatile general anesthetics.

neuroscience↗

bioRxiv2020

A conserved role for sleep in supporting spatial learning in Drosophila

Sleep loss and aging impair hippocampus-dependent spatial learning in mammalian systems. Here we use the fly Drosophila melanogaster to investigate the relationship between sleep and spatial learning in healthy and impaired flies. The spatial learning assay is modeled after the Morris Water Maze. The assay uses a thermal maze consisting of a 5x5 grid of Peltier plates maintained at 36-37{degrees}C and a visual panorama. The first trial begins when a single tile that is associated with a specific visual cue is cooled to 25{degrees}C. For subsequent trials, the cold tile is heated, the visual panorama is rotated and the flies must find the new cold-tile by remembering its association with the visual cue. Significant learning was observed with two different wild-type strains - Cs and 2U, validating our design. Sleep deprivation prior to training impaired spatial learning. Learning was also impaired in the classic learning mutant rutabaga (rut); enhancing sleep restored learning to rut mutants. Further we found that flies exhibited dramatic age-dependent cognitive decline in spatial learning starting at 20-24 days of age. These impairments could be reversed by enhancing sleep. Finally, we find that spatial learning requires dopaminergic signaling and that enhancing dopaminergic signaling in aged flies restored learning. Our results are consistent with the impairments seen in rodents and humans. These results thus demonstrate a critical conserved role for sleep in supporting spatial learning, and suggest potential avenues for therapeutic intervention during aging. STATEMENT OF SIGNIFICANCEWe have studied the relationship between sleep and plasticity using a Drosophila learning assay modified after the Morris Water Maze. Using this assay, we find that sleep loss impairs spatial learning. As in mammals, flies exhibited age-dependent spatial learning impairments. Importantly, the age-dependent impairments were reversed by enhancing sleep. Interestingly, our results mirror studies on hippocampus dependent memories in rodents and humans. Thus, our data describe an evolutionarily conserved role for sleep in regulating spatial learning. They also support augmenting sleep as a therapeutic strategy to ameliorate learning impairments.

neuroscience↗

bioRxiv2020

Integrated information structure collapses with anesthetic loss of conscious arousal in Drosophila melanogaster

The physical basis of consciousness remains one of the most elusive concepts in current science. One influential conjecture is that consciousness is to do with some form of causality, measurable through information. The integrated information theory of consciousness (IIT) proposes that conscious experience, filled with rich and specific content, corresponds directly to a hierarchically organised, irreducible pattern of causal interactions; i.e. an integrated informational structure among elements of a system. Here, we tested this conjecture in a simple biological system (fruit flies), estimating the information structure of the system during wakefulness and general anesthesia. Consistent with this conjecture, we found that integrated interactions among populations of neurons during wakefulness collapsed to isolated clusters of interactions during anesthesia. We used classification analysis to quantify the accuracy of discrimination between wakeful and anesthetised states, and found that informational structures inferred conscious states with greater accuracy than a scalar summary of the structure, a measure which is generally championed as the main measure of IIT. In stark contrast to a view which assumes feedforward architecture for insect brains, especially fly visual systems, we found rich information structures, which cannot arise from purely feedforward systems, occurred across the fly brain. Further, these information structures collapsed uniformly across the brain during anesthesia. Our results speak to the potential utility of the novel concept of an "informational structure" as a measure for level of consciousness, above and beyond simple scalar values. Author summaryThe physical basis of consciousness remains elusive. Efforts to measure consciousness have generally been restricted to simple, scalar quantities which summarise the complexity of a system, inspired by integrated information theory, which links a multi-dimensional, informational structure to the contents of experience in a system. Due to the complexity of the definition of the structure, assessment of its utility as a measure of conscious arousal in a system has largely been ignored. In this manuscript we evaluate the utility of such an information structure in measuring the level of arousal in the fruit fly. Our results indicate that this structure can be more informative about the level of arousal in a system than even the single-value summary proposed by the theory itself. These results may push consciousness research towards the notion of multi-dimensional informational structures, instead of traditional scalar summaries.

neuroscience↗

bioRxiv2019

{-}{-} Downregulation of a satiety signal from peripheral fat bodies improves visual attention while reducing sleep need in Drosophila .

Sleep is vital for survival. Yet, under environmentally challenging conditions such as starvation, animals suppress their need for sleep. Interestingly, starvation-induced sleep loss does not evoke a subsequent sleep rebound. Little is known about how starvation-induced sleep deprivation differs from other types of sleep loss, or why some sleep functions become dispensable during starvation. Here we demonstrate that downregulation of unpaired-2 (upd2, the Drosophila ortholog of leptin), is sufficient to mimic a starved-like state in flies. We use this genetically starved state to investigate the consequences of a starvation signal on visual attention and sleep in otherwise well-fed flies, thereby sidestepping the negative side-effects of undernourishment. We find that knockdown of upd2 in the fat body is sufficient to suppress sleep while also increasing selective visual attention and promoting night-time feeding. Further, we show that this peripheral signal is integrated in the fly brain via insulin-expressing cells. Together, these findings identify a role for peripheral tissue-to-brain interactions in the simultaneous regulation of sleep and attention, to potentially promote adaptive behaviors necessary for survival in hungry animals.\n\nAuthor SummarySleep is important for maintaining both physiological (e.g., metabolic, immunological, and developmental) and cognitive processes, such as selective attention. Under nutritionally impoverished conditions, animals suppress sleep and increase foraging to locate food. Yet it is currently unknown how an animal is able to maintain well-tuned cognitive processes, despite being sleep deprived. Here we investigate this question by studying flies that have been genetically engineered to lack a satiety signal, and find that signaling from fat bodies in the periphery to insulin-expressing cells in the brain simultaneously regulates sleep need and attention-like processes.

neuroscience↗

bioRxiv2018

Sleep regulates visual selective attention in Drosophila

Although sleep-deprivation is known to impair attention in humans and other mammals, the underlying reasons are not well understood, and whether similar effects are present in non-mammalian species is not known. We therefore sought to investigate whether sleep is important for optimising attention in an invertebrate species, the genetic model Drosophila melanogaster. We developed a high-throughput paradigm to measure visual attention in freely-walking Drosophila, using competing foreground/background visual stimuli. We found that whereas sleep-deprived flies could respond normally to either stimulus alone, they were more distracted by background cues in a visual competition task. Other stressful manipulations such as starvation, heat exposure, and mechanical stress had no effects on visual attention in this paradigm. In contrast to sleep-deprivation, providing additional sleep using the GABA-A agonist 4,5,6,7-tetrahydroisoxazolo-[5,4-c]pyridine-3-ol (THIP) did not affect attention in wild-type flies, but significantly improved attention in the learning mutant dunce. Our results reveal a key function of sleep in optimising attention processes in Drosophila, and establish a behavioural paradigm that can be used to explore the molecular mechanisms involved.\n\nSummary statementSleep deprivation specifically impairs visual selective attention in fruit flies, without affecting behavioural responses to simple visual stimuli.

animal behavior and cognition↗

bioRxiv2018

Innate visual preferences and behavioral flexibility in Drosophila

Visual decision-making in animals is influenced by innate preferences as well as experience. Interaction between hard-wired responses and changing motivational states determines whether a visual stimulus is attractive, aversive, or neutral. It is however difficult to separate the relative contribution of nature versus nurture in experimental paradigms, especially for more complex visual parameters such as the shape of objects. We used a closed-loop virtual reality paradigm for walking Drosophila flies to uncover innate visual preferences for the shape and size of objects, in a recursive choice scenario allowing the flies to reveal their visual preferences over time. We found that Drosophila flies display a robust attraction / repulsion profile for a range of objects sizes in this paradigm, and that this visual preference profile remains evident under a variety of conditions and persists into old age. We also demonstrate a level of flexibility in this behavior: innate repulsion to certain objects could be transiently overridden if these were novel, although this effect was only evident in younger flies. Finally, we show that a reward circuit in the fly brain, Drosophila neuropeptide F (dNPF), can be recruited to guide visual decision-making. Optogenetic activation of dNPF-expressing neurons converted a visually repulsive object into a more attractive object. This suggests that dNPF activity in the Drosophila brain guides ongoing visual choices, to override innate preferences and thereby provide a necessary level of behavioral flexibility in visual decision-making.

animal behavior and cognition↗

bioRxiv2017

Isoflurane reduces feedback in the fruit fly brain

Hierarchically organized brains communicate through feedforward and feedback pathways. In mammals, feedforward and feedback are mediated by higher and lower frequencies during wakefulness. Feedback is preferentially impaired by general anesthetics. This suggests feedback serves critical functions in waking brains. The brain of Drosophila melanogaster (fruit fly) is also hierarchically organized, but the presence of feedback in these brains is not established. Here we studied feedback in the fruit fly brain, by simultaneously recording local field potentials (LFPs) from low-order peripheral structures and higher-order central structures. Directed connectivity analysis revealed that low frequencies (0.1-5Hz) mediated feedback from the center to the periphery, while higher frequencies (10-45Hz) mediated feedforward in the opposite direction. Further, isoflurane anesthesia preferentially reduced feedback. Our results imply that similar spectral characteristics of feedforward and feedback may be a signature of hierarchically organized brains and that general anesthetics may induce unresponsiveness by targeting the mechanisms that support feedback.

neuroscience↗