Leonie Kirszenblat

Sleep is a state of reduced behavioural responsiveness to the external world. Lowered arousal is thought to arise from sensory gating in the brain, yet there is compelling evidence that stimuli can still be processed to some degree. Which aspects of sensory information are processed during sleep remains largely unknown. Here, we perform comprehensive recordings of activity from multiple neuron types during sleep and wakefulness in the Drosophila olfactory association center. We find that baseline activity of dopamine neurons (DANs) is distinct between active, rest and sleep states, enabling a decoder to predict when the fly is asleep. Optogenetic inhibition of DANs acutely induces sleep and lowers odor-evoked arousal, suggesting causality between DAN activity and behavior. We then examine odor processing during sleep, and find that whereas coding of odor identity in Kenyon cells (KCs) remains intact, coding of odor value in DANs is altered. Specifically, DANs encoding positive (attractive) and negative (aversive) values change their odor responses in an opposing manner, producing more aversive odor representations during sleep. Consistent with these changes in neural activity, sleeping flies awoken by odors show reduced approach and increased avoidance behaviour. Taken together, our data reveal that the brain does not simply suppress the propagation of sensory signals during sleep; rather, it utilizes different cell types to retain or modify specific aspects of sensory information. The aversive odor evaluation in DANs may have ethological benefits as it suppresses the motivation to pursue attractive odors during sleep and primes defensive action when aroused by the scent of potential dangers.

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 down-regulation of the secreted cytokine unpaired 2 (upd2) in Drosophila flies may mimic a starved-like state. We used a genetic knockdown strategy to investigate the consequences of upd2 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 (FB) is sufficient to suppress sleep and promote feeding-related behaviors while also improving selective visual attention. Furthermore, 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 quality and attention, to potentially promote adaptive behaviors necessary for survival in hungry animals.

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. Author Summary: Sleep 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.

Sleep optimizes waking behavior, however, waking experience may also influence sleep. We used the fruit fly Drosophila melanogaster to investigate the relationship between visual experience and sleep in wild-type and mutant flies. We found that the classical visual mutant, optomotor-blind (omb), which has undeveloped horizontal system/vertical system (HS/VS) motion-processing cells and are defective in motion and visual salience perception, showed dramatically reduced and less consolidated sleep compared to wild-type flies. In contrast, optogenetic activation of the HS/VS motion-processing neurons in wild-type flies led to an increase in sleep following the activation, suggesting an increase in sleep pressure. Surprisingly, exposing wild-type flies to repetitive motion stimuli for extended periods did not increase sleep pressure. However, we observed that exposing flies to more complex image sequences from a movie led to more consolidated sleep, particularly when images were randomly shuffled through time. Our results suggest that specific forms of visual experience that involve motion circuits and complex, nonrepetitive imagery, drive sleep need in Drosophila.

The dopamine ontogeny hypothesis for schizophrenia proposes that transient dysregulation of the dopaminergic system during brain development increases the likelihood of this disorder in adulthood. To test this hypothesis in a high throughput animal model, we have transiently manipulated dopamine signaling in the developing fruit fly Drosophila melanogaster and examined behavioral responsiveness in adult flies. We found that either a transient increase of dopamine neuron activity or a transient decrease of dopamine receptor expression during fly brain development permanently impairs behavioral responsiveness in adults. A screen for impaired responsiveness revealed sleep-promoting neurons in the central brain as likely post-synaptic dopamine targets modulating these behavioral effects. Transient dopamine receptor knockdown during development in a restricted set of ~20 sleep-promoting neurons recapitulated the dopamine ontogeny phenotype, by permanently reducing responsiveness in adult animals. This suggests that disorders involving impaired behavioral responsiveness might result from defective ontogeny of sleep/wake circuits.

The University of Queensland's institutional repository, UQ eSpace, aims to create global visibility and accessibility of UQ’s scholarly research.

Neurexins are cell adhesion molecules that are important for synaptic plasticity and homeostasis, although links to sleep have not yet been investigated. We examined the effects of neurexin‐1 perturbation on sleep in Drosophila, showing that neurexin‐1 nulls displayed fragmented sleep and altered circadian rhythm. Conversely, the over‐expression of neurexin‐1 could increase and consolidate night‐time sleep. This was not solely due to developmental effects as it could be induced acutely in adulthood, and was coupled with evidence of synaptic growth. The timing of over‐expression could differentially impact sleep patterns, with specific night‐time effects. These results show that neurexin‐1 was dynamically involved in synaptic plasticity and sleep in Drosophila. Neurexin‐1 and a number of its binding partners have been repeatedly associated with mental health disorders, including autism spectrum disorders, schizophrenia and Tourette syndrome, all of which are also linked to altered sleep patterns. How and when plasticity‐related proteins such as neurexin‐1 function during sleep can provide vital information on the interaction between synaptic homeostasis and sleep, paving the way for more informed treatments of human disorders.

A crucial function of the brain is to be able to distinguish whether or not changes in the environment are caused by one9s own actions. Even the smallest brains appear to be capable of making this distinction, as has been shown by closed-loop behavioral experiments in flies controlling visual stimuli in virtual reality paradigms. We questioned whether activity in the fruit fly brain is different during such closed-loop behavior, compared with passive viewing of a stimulus. To address this question, we used a procedure to record local field potential (LFP) activity across the fly brain while flies were controlling a virtual object through their movement on an air-supported ball. The virtual object was flickered at a precise frequency (7 Hz), creating a frequency tag that allowed us to track brain responses to the object while animals were behaving. Following experiments under closed-loop control, we replayed the same stimulus to the fly in open loop, such that it could no longer control the stimulus. We found identical receptive fields and similar strength of frequency tags across the brain for the virtual object under closed loop and replay. However, when comparing central versus peripheral brain regions, we found that brain responses were differentially modulated depending on whether flies were in control or not. Additionally, coherence of LFP activity in the brain increased when flies were in control, compared with replay, even if motor behavior was similar. This suggests that processes associated with closed-loop control promote temporal coordination in the insect brain. SIGNIFICANCE STATEMENT We show that closed-loop control of a visual stimulus promotes temporal coordination across the Drosophila brain, compared with open-loop replay of the same visual sequences. This is significant because it suggests that, to understand goal-directed behavior or visual attention in flies, it may be most informative to sample neural activity from multiple regions across the brain simultaneously, and to examine temporal relationships (e.g., coherence) between these regions.