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

Dissel, Stephane; Klose, Markus K.; Swinderen, Bruno van; Cao, Lijuan; Ford, Melanie C.; Periandri, Erica M.; Jones, Joseph D; Li, Zhaoyi; Shaw, Paul J.

doi:10.1371/journal.pbio.3001797

Cited by 9 publications

(9 citation statements)

References 97 publications

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“…Thus, we hypothesized 060B, PPL1-γ2,α1, PPL1-α’2α2, PPL1-α’3 and PPL1-α3-projecting DANs may display changes in activity in the AM vs. PM. To test this hypothesis, we expressed the cyclic adenosine monophosphate (cAMP) sensor, UAS- Epac1-camps , in 060B neurons and used high throughput live brain imaging to monitor neuronal responses to bath-applied DA in the AM or PM from cell bodies (Figure 2I) ( 14, 96, 97 ). As seen in Figure 2I-J, 060B cell bodies showed robust increases in FRET signaling in the AM compared to the PM.…”

Section: Resultsmentioning

confidence: 99%

Breaking free from the clock’s tyranny restores memory to brain damaged flies

Dissel,

Morgan,

Cao

et al. 2024

Preprint

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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 neuromodulation's key role in cognitive restoration, where sleep aids memory in damaged brains, but a functioning clock unexpectedly hinders this process.

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Section: Resultsmentioning

confidence: 99%

Breaking free from the clock’s tyranny restores memory to brain damaged flies

Dissel,

Morgan,

Cao

et al. 2024

Preprint

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“…Why, then, does this protocol not cause an effect in dFB 23E10□84C10 neurons? Previous studies have demonstrated that the dFB is under strong dopaminergic inhibition (15, 17, 20, 44) and that dopamine is a key factor regulating whether dFB neurons are active or silent (20). In addition, it was shown that sleep deprivation increases the activity of dFB neurons, switching them to the active state (16).…”

Section: Resultsmentioning

confidence: 99%

The dorsal fan-shaped body is a neurochemically heterogeneous sleep-regulating center inDrosophila

Jones,

Holder,

Montgomery

et al. 2024

Preprint

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Sleep is a behavior that is conserved throughout the animal kingdom. Yet, despite extensive studies in humans and animal models, the exact function or functions of sleep remain(s) unknown. A complicating factor in trying to elucidate the function of sleep is the complexity and multiplicity of neuronal circuits that are involved in sleep regulation. It is conceivable that distinct sleep-regulating circuits are only involved in specific aspects of sleep and may underlie different sleep functions. Thus, it would be beneficial to assess the contribution of individual circuits in sleep’s putative functions. The intricacy of the mammalian brain makes this task extremely difficult. However, the fruit flyDrosophila melanogaster,with its simpler brain organization, available connectomics, and unparalleled genetics offers the opportunity to interrogate individual sleep-regulating centers. InDrosophila, neurons projecting to the dorsal Fan-Shaped Body (dFB) have been proposed to be key regulators of sleep, particularly sleep homeostasis. We recently demonstrated that the most widely used genetic tool to manipulate dFB neurons, the 23E10-GAL4 driver, expresses in two sleep-regulating neurons (VNC-SP neurons) located in the Ventral Nerve Cord (VNC), the fly analog of the vertebrate spinal cord. Since most data supporting a role for the dFB in sleep regulation have been obtained using 23E10-GAL4, it is unclear whether the sleep phenotypes reported in these studies are caused by dFB neurons or VNC-SP cells. A recent publication replicated our finding that 23E10-GAL4 contains sleep-promoting neurons in the VNC. However, it also proposed that the dFB is not involved in sleep regulation at all. Unfortunately, this suggestion was made using genetic tools that are not dFB-specific. In this study, using a newly created dFB-specific genetic driver line, we demonstrate that the majority of 23E10-GAL4 dFB neurons can promote sleep when activated and that these neurons are involved in sleep homeostasis. In addition, we show that dFB neurons are neurochemically heterogeneous. Most dFB neurons express both glutamate and acetylcholine, while a minority of cells express only one of these two neurotransmitters. Importantly, dFB neurons do not express GABA, as previously suggested. Using neurotransmitter-specific dFB tools, our data also points at cholinergic dFB neurons as particularly potent at promoting sleep. Finally, we demonstrate that dFB-induced sleep can consolidate Short-Term Memory (STM) into Long-Term Memory (LTM), suggesting that the benefit of sleep on memory is not circuit-specific.

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“…Similarly, the Dopamine 1-like receptor 1 ( Dop1R1 ) is not expressed in the sleep-promoting dorsal Fan Shaped Body neurons in healthy adults [86]. However, following starvation or time restricted feeding the Dop1R1 is recruited to the dorsal Fan Shaped body to provide additional inhibitory tone to sleep promoting neurons [87]. Finally, a sleep circuit that is primarily active during a narrow developmental time-window can be reactivated in adults when flight is impaired [88].…”

Section: Discussionmentioning

confidence: 99%

Sleep Deprivation, Sleep Fragmentation and Social Jet Lag increase temperature preference inDrosophila

Roach

Ford

Simhambhatla

et al. 2023

Preprint

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Despite the fact that sleep deprivation substantially affects the way animals regulate their body temperature, the specific mechanisms behind this phenomenon are not well understood. In both mammals and flies, neural circuits regulating sleep and thermoregulation overlap, suggesting an interdependence that may be relevant for sleep function. To investigate this relationship further, we exposed flies to 12 h of sleep deprivation, or 48 h of sleep fragmentation and evaluated temperature preference in a thermal gradient. Flies exposed to 12 h of sleep deprivation chose warmer temperatures after sleep deprivation. Importantly, sleep fragmentation, which prevents flies from entering deeper stages of sleep, but does not activate sleep homeostatic mechanisms nor induce impairments in short-term memory also resulted in flies choosing warmer temperatures. To identify the underlying neuronal circuits, we used RNAi to knock down the receptor forPigment dispersing factor, a peptide that influences circadian rhythms, temperature preference and sleep. Expressing UAS-PdfrRNAiin subsets of clock neurons prevented sleep fragmentation from increasing temperature preference. Finally, we evaluated temperature preference after flies had undergone a social jet lag protocol which is known to disrupt clock neurons. In this protocol, flies experience a 3 h light phase delay on Friday followed by a 3 h light advance on Sunday evening. Flies exposed to social jet lag exhibited an increase in temperature preference which persisted for several days. Our findings identify specific clock neurons that are modulated by sleep disruption to increase temperature preference. Moreover, our data indicate that temperature preference may be a more sensitive indicator of sleep disruption than learning and memory.

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

Cited by 9 publications

References 97 publications

Breaking free from the clock’s tyranny restores memory to brain damaged flies

Breaking free from the clock’s tyranny restores memory to brain damaged flies

The dorsal fan-shaped body is a neurochemically heterogeneous sleep-regulating center inDrosophila

Sleep Deprivation, Sleep Fragmentation and Social Jet Lag increase temperature preference inDrosophila

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